Difference between revisions of "2023 AMS-535 Fall"

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== '''Class Schedule''' ==
 
{| align="center" border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:95%"
 
{| align="center" border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:95%"
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|- style="background:cornflowerblue"
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| <center>'''Date'''</center>
 +
| <center>'''Topic'''</center>
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| <center>'''Speaker and Presentation'''</center>
 +
| <center>'''Primary Reference'''</center>
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| <center>'''Secondary Reference'''</center>
 
|-
 
|-
  | <center>'''Date'''</center>
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  | <center>'''Topic'''</center>
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| <center>2023.08.28 Mon</center>
  | <center>'''Speaker and Presentation'''</center>
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||
  | <center>'''Primary Reference'''</center>
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*''Organizational Meeting''
  | <center>'''Secondary Reference'''</center>
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||[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.28.ams535.rizzo.organizational.mp4 Rizzo, R. mp4]
 +
|| Course introduction and format.  Go over Syllabus.  Course participant background and introductions.
 +
|| <center>-</center>
 
|-
 
|-
  | <center>2023.08.28 Mon</center>
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  | *''Organizational Meeting''
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| <center>2023.08.30 Wed</center>
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.28.ams535.rizzo.organizational.mp4 Rizzo, R. mp4]
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||
  | Course introduction and format.  Go over Syllabus.  Course participant background and introductions.
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'''SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE'''
  | <center>-</center>
 
|-
 
  | <center>2023.08.30 Wed</center>
 
  | '''SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE'''
 
 
*''Drug Discovery''
 
*''Drug Discovery''
 
# Introduction, history, irrational vs. rational
 
# Introduction, history, irrational vs. rational
 
# Viral Target Examples
 
# Viral Target Examples
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001.mp4 Rizzo, R. mp4]
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 +
||
 +
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001.mp4 Rizzo, R. mp4]
 
<br>
 
<br>
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001.pdf Rizzo, R. pdf] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001_pdfhandouts.pdf pdf_handout]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001.pdf Rizzo, R. pdf] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.08.30.ams535.rizzo.lect.001_pdfhandouts.pdf pdf_handout]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen009.pdf Jorgensen, W.L., The many roles of computation in drug discovery. ''Science'' '''2004''', ''303'', 1813-8]
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||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen009.pdf Jorgensen, W.L., The many roles of computation in drug discovery. ''Science'' '''2004''', ''303'', 1813-8]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kuntz004.pdf Kuntz, I. D., Structure-based strategies for drug design and discovery. ''Science'' '''1992''', ''257'', 1078-1082]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kuntz004.pdf Kuntz, I. D., Structure-based strategies for drug design and discovery. ''Science'' '''1992''', ''257'', 1078-1082]
  | <center>-</center>
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|| <center>-</center>
 
|-
 
|-
  | <center>2023.09.04 Mon</center>
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  | *''No Class: Labor Day''
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|- style="background:peachpuff"
  | <center>-</center>
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| <center>2023.09.04 Mon</center>
  | <center>-</center>
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||
  | <center>-</center>
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*''No Class: Labor Day''
 +
||<center>-</center>
 +
||<center>-</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.09.06 Wed</center>
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| <center>2023.09.06 Wed</center>
  | *''Chemistry Review''
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||
 +
*''Chemistry Review''
 
# Molecular structure, bonding, graphical representations  
 
# Molecular structure, bonding, graphical representations  
# Functionality, properties of organic molecules
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# Functionality, properties of organic molecules  
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.06.ams535.rizzo.lect.002.mp4 Rizzo, R. mp4]
+
 
 +
||
 +
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.06.ams535.rizzo.lect.002.mp4 Rizzo, R. mp4]
 
<br>
 
<br>
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.06.ams535.rizzo.lect.002.pdf Rizzo, R. pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.06.ams535.rizzo.lect.002.pdf Rizzo, R. pdf]
  | <center>in class lecture</center>
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|| <center>in class lecture</center>
  | <center>-</center>
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|| <center>-</center>
 
|-
 
|-
  | <center>2023.09.11 Mon</center>
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  | *''Biomolecular Structure''
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| <center>2023.09.11 Mon</center>
 +
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 +
*''Biomolecular Structure''
 
:1. Lipids, carbohydrates  
 
:1. Lipids, carbohydrates  
:2. Nucleic acids, proteins
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:2. Nucleic acids, proteins
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.11.ams535.rizzo.lect.003.mp4 Rizzo, R. mp4]
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 +
||
 +
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.11.ams535.rizzo.lect.003.mp4 Rizzo, R. mp4]
 
<br>
 
<br>
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.11.ams535.rizzo.lect.003.pdf Rizzo, R. pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.11.ams535.rizzo.lect.003.pdf Rizzo, R. pdf]
  | <center>in class lecture</center>
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|| <center>in class lecture</center>
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/2010.amino_acids_scanned.pdf structures of the 20 amino acid side chains]
+
|| [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/2010.amino_acids_scanned.pdf structures of the 20 amino acid side chains]
 
|-
 
|-
  | <center>2023.09.13 Wed</center>
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  | *''Molecular Interactions and Recognition''
+
 
 +
| <center>2023.09.13 Wed</center>
 +
||
 +
*''Molecular Interactions and Recognition''
 
:1. Electrostatics, VDW interactions, hydrophobic effect, molecular recognition (binding energy)
 
:1. Electrostatics, VDW interactions, hydrophobic effect, molecular recognition (binding energy)
:2. Inhibitors types: allosteric, transition state, covalent vs non-covalent, selective, competitive
+
:2. Inhibitors types: allosteric, transition state, covalent vs non-covalent, selective, competitive
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.13.ams535.rizzo.lect.004.mp4 Rizzo, R. mp4]
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||
 +
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.13.ams535.rizzo.lect.004.mp4 Rizzo, R. mp4]
 
<br>
 
<br>
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.13.ams535.rizzo.lect.004.pdf Rizzo, R. pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.13.ams535.rizzo.lect.004.pdf Rizzo, R. pdf]
  | <center>in class lecture</center>
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|| <center>in class lecture</center>
  | <center>-</center>
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|| <center>-</center>
 
|-
 
|-
  | <center>2023.09.18 Mon</center>
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  | *''Intro. to Methods in 3-D Structure Determination''
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| <center>2023.09.18 Mon</center>
 +
||
 +
*''Intro. to Methods in 3-D Structure Determination''
 
:1. Crystallography, NMR  
 
:1. Crystallography, NMR  
:2. Structure Quality, PDB in detail
+
:2. Structure Quality, PDB in detail  
  | [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.18.ams535.rizzo.lect.005.mp4 Rizzo, R. mp4]
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||
 +
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.18.ams535.rizzo.lect.005.mp4 Rizzo, R. mp4]
 
<br>
 
<br>
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.18.ams535.rizzo.lect.005.pdf Rizzo, R. pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.18.ams535.rizzo.lect.005.pdf Rizzo, R. pdf]
  | <center>in class lecture</center>
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|| <center>in class lecture</center>
  | <center>-</center>
+
|| <center>-</center>
 
|-
 
|-
  | <center>-</center>
+
 
  | <center>-</center>
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|- style="background:lightgreen"
  | <center>-</center>
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| <center>-</center>
  | <center>'''IN CLASS QUIZ for Section 1 2023.09.20 WED'''</center>
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||<center>-</center>
  | <center>-</center>
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||<center>-</center>
 +
||<center>'''IN CLASS QUIZ for Section 1 2023.09.20 WED'''</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.09.20 Wed </center>
+
 
  | QUIZ #1 FIRST 30 MINUTES  
+
| <center>2023.09.20 Wed </center>
 +
|| QUIZ #1 FIRST 30 MINUTES  
 
'''SECTION II: MOLECULAR MODELING'''
 
'''SECTION II: MOLECULAR MODELING'''
 
* ''Classical Force Fields''
 
* ''Classical Force Fields''
 
:1. All-atom Molecular Mechanics
 
:1. All-atom Molecular Mechanics
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.20.AMS535.talk01.mp4 Alseika, Zachary mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.20.AMS535.talk01.pdf  pdf]
+
|| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.20.AMS535.talk01.mp4 Alseika, Zachary mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.20.AMS535.talk01.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Mackerell001.pdf Mackerell, A. D., Jr., Empirical force fields for biological macromolecules: overview and issues. ''J. Comput. Chem.'' '''2004''', ''25'', 1584-604]
+
 
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/vangunsteren003.pdf van Gunsteren, W. F.; et al., Biomolecular modeling: Goals, problems, perspectives. ''Angew. Chem. Int. Ed. Engl.'' '''2006''', ''45'', 4064-92]
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|
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Mackerell001.pdf Mackerell, A. D., Jr., Empirical force fields for biological macromolecules: overview and issues. ''J. Comput. Chem.'' '''2004''', ''25'', 1584-604]
 +
|
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/vangunsteren003.pdf van Gunsteren, W. F.; et al., Biomolecular modeling: Goals, problems, perspectives. ''Angew. Chem. Int. Ed. Engl.'' '''2006''', ''45'', 4064-92]
 
|-
 
|-
  | <center>2023.09.25 Mon</center>
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| <center>2023.09.25 Mon</center>
  | * ''Classical Force Fields''
+
|
 +
* ''Classical Force Fields''
 
:1. OPLS
 
:1. OPLS
 
:2. AMBER
 
:2. AMBER
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.mp4 S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.pdf  pdf]
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| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.mp4 S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.pdf  pdf]
 
<br>
 
<br>
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk02.mp4 S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk02.pdf  pdf]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk02.mp4 S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen002.pdf Jorgensen, W. L.; et al., Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. ''J. Am. Chem. Soc.'' '''1996''', ''118'', 11225-11236]
+
 
 +
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen002.pdf Jorgensen, W. L.; et al., Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. ''J. Am. Chem. Soc.'' '''1996''', ''118'', 11225-11236]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman004.pdf Cornell, W. D.; et al., A Second Generation Force Field For the Simulation of Proteins, Nucleic Acids, and Organic Molecules. ''J. Am. Chem. Soc.'' '''1995''', ''117'', 5179-5197]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman004.pdf Cornell, W. D.; et al., A Second Generation Force Field For the Simulation of Proteins, Nucleic Acids, and Organic Molecules. ''J. Am. Chem. Soc.'' '''1995''', ''117'', 5179-5197]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen004.pdf Jorgensen, W. L.; et al., The Opls Potential Functions For Proteins - Energy Minimizations For Crystals of Cyclic-Peptides and Crambin. ''J. Am. Chem. Soc.'' '''1988''', ''110'', 1657-1671]
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| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen004.pdf Jorgensen, W. L.; et al., The Opls Potential Functions For Proteins - Energy Minimizations For Crystals of Cyclic-Peptides and Crambin. ''J. Am. Chem. Soc.'' '''1988''', ''110'', 1657-1671]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman005.pdf Bayly, C. I.; et al., A Well-Behaved Electrostatic Potential Based Method Using Charge Restraints For Deriving Atomic Charges - the RESP Model. ''J. Phys. Chem.'' '''1993''', ''97'', 10269-10280]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman005.pdf Bayly, C. I.; et al., A Well-Behaved Electrostatic Potential Based Method Using Charge Restraints For Deriving Atomic Charges - the RESP Model. ''J. Phys. Chem.'' '''1993''', ''97'', 10269-10280]
 
|-
 
|-
  | <center>2023.09.27 Wed </center>
+
| <center>2023.09.27 Wed </center>
  | *''Explicit Solvent Models''
+
|
 +
*''Explicit Solvent Models''
 
:1. Water models (TIP3P, TIP4P, SPC)
 
:1. Water models (TIP3P, TIP4P, SPC)
 
:2. Condensed-phase calculations (DGhydration)
 
:2. Condensed-phase calculations (DGhydration)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk01.mp4  S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk01.pdf  pdf]
+
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk01.mp4  S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk01.pdf  pdf]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk02.mp4 S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk02.pdf  pdf]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk02.mp4 S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen003.pdf Jorgensen, W. L.; et al., Comparison of Simple Potential Functions for Simulating Liquid Water. ''J. Chem. Phys.'' '''1983''', ''79'', 926-935]
+
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen003.pdf Jorgensen, W. L.; et al., Comparison of Simple Potential Functions for Simulating Liquid Water. ''J. Chem. Phys.'' '''1983''', ''79'', 926-935]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen010.pdf Jorgensen, W. L.;  et al., Monte Carlo Simulation of Differences in Free Energies of Hydration. ''J. Chem. Phys.'' '''1985''', ''83'', 3050-3054]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen010.pdf Jorgensen, W. L.;  et al., Monte Carlo Simulation of Differences in Free Energies of Hydration. ''J. Chem. Phys.'' '''1985''', ''83'', 3050-3054]
  | 2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/DDGhyd_cycle.pdf Thermodynamic Cycle as Drawn By Dr. Rizzo]
+
| 2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/DDGhyd_cycle.pdf Thermodynamic Cycle as Drawn By Dr. Rizzo]
 +
 
 
|-
 
|-
  | <center>2023.10.02 Mon</center>
+
| <center>2023.10.02 Mon</center>
  | *''Continuum Solvent Models''
+
|
 +
*''Continuum Solvent Models''
 
:1. Generalized Born Surface Area (GBSA)
 
:1. Generalized Born Surface Area (GBSA)
 
:2. Poisson-Boltzmann Surface Area (PBSA)
 
:2. Poisson-Boltzmann Surface Area (PBSA)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk01.mp4  S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk01.pdf  pdf]
+
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk01.mp4  S1 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk01.pdf  pdf]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk02.mp4  S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk02.pdf  pdf]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk02.mp4  S2 mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.02.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Still001.pdf Still, W. C.; et al., Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. ''J. Am. Chem. Soc'' 1990, ''112'', 6127-6129]
+
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Still001.pdf Still, W. C.; et al., Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. ''J. Am. Chem. Soc'' 1990, ''112'', 6127-6129]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Honig001.pdf Sitkoff, D.; et al., Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models. ''J. Phys. Chem.'' '''1994''', ''98'', 1978-1988]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Honig001.pdf Sitkoff, D.; et al., Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models. ''J. Phys. Chem.'' '''1994''', ''98'', 1978-1988]
  | <center>-</center>
+
| <center>-</center>
 +
|-
 +
<center>-</center>
 
|-
 
|-
  | <center>-</center>
+
 
  | <center>-</center>
+
|- style="background:lightgreen"
  | <center>-</center>
+
| <center>-</center>
  | <center>'''IN CLASS QUIZ for Section 2 2023.10.04 WED'''</center>
+
||<center>-</center>
  | <center>'''Additional resources:'''</center>
+
||<center>-</center>
 +
||<center>'''IN CLASS QUIZ for Section 2 2023.10.04 WED'''</center>
 +
||<center>'''Additional resources:'''</center>
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Duarte01.pdf Duarte Ramos Matos, G.; et al., Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database. ''J. Chem. Eng. Data'' '''2017''', ''62'', 1559-1569] <br>  
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Duarte01.pdf Duarte Ramos Matos, G.; et al., Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database. ''J. Chem. Eng. Data'' '''2017''', ''62'', 1559-1569] <br>  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Loeffler01.pdf Loeffler, H. H.; et al., Reproducibility of Free Energy Calculations across Different Molecular Simulation Software Packages ''J. Chem. Theory Comput.'' '''2018''', ''14'', 5567−5582]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Loeffler01.pdf Loeffler, H. H.; et al., Reproducibility of Free Energy Calculations across Different Molecular Simulation Software Packages ''J. Chem. Theory Comput.'' '''2018''', ''14'', 5567−5582]
 
|-
 
|-
  | <center>2023.10.04 Wed </center>
+
 
  | '''SECTION III: SAMPLING METHODS'''
+
| <center>2023.10.04 Wed </center>
 +
||
 +
'''SECTION III: SAMPLING METHODS'''
 
*''Molecular Conformations''
 
*''Molecular Conformations''
 
:1. Small molecules, peptides, relative energy, minimization methods
 
:1. Small molecules, peptides, relative energy, minimization methods
 
*''Sampling Methods for Large Simulations''
 
*''Sampling Methods for Large Simulations''
:2. Molecular dynamics (MD)
+
:2. Molecular dynamics (MD)  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.mp4  S1 mp4]
+
 
 +
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman011.pdf Howard, A. E.; Kollman, P. A., An analysis of current methodologies for conformational searching of complex molecules. ''J. Med. Chem.'' '''1988''', ''31'', 1669-75]
+
 
 +
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman011.pdf Howard, A. E.; Kollman, P. A., An analysis of current methodologies for conformational searching of complex molecules. ''J. Med. Chem.'' '''1988''', ''31'', 1669-75]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Petsko001.pdf Karplus, M.; Petsko, G. A., Molecular dynamics simulations in biology. ''Nature'' '''1990''', ''347'', 631-9]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Petsko001.pdf Karplus, M.; Petsko, G. A., Molecular dynamics simulations in biology. ''Nature'' '''1990''', ''347'', 631-9]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Colby_College_MMtutor.pdf Section 4 (PAGES 22-27) Colby College Molecular Mechanics Tutorial Introduction, 2004, Shattuck, T.W., Colby College]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Colby_College_MMtutor.pdf Section 4 (PAGES 22-27) Colby College Molecular Mechanics Tutorial Introduction, 2004, Shattuck, T.W., Colby College]
  
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Holloway001.pdf Holloway, M. K., A priori prediction of ligand affinity by energy minimization. ''Perspect. Drug Discov. Design'' '''1998''', ''9-11'', 63-84]
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Holloway001.pdf Holloway, M. K., A priori prediction of ligand affinity by energy minimization. ''Perspect. Drug Discov. Design'' '''1998''', ''9-11'', 63-84]
 
|-
 
|-
  | <center>2023.10.09 Mon</center>
+
|- style="background:peachpuff"
  | *''No Class: Fall Break''
+
| <center>2023.10.09 Mon</center>
  | <center>-</center>
+
||
  | <center>-</center>
+
*''No Class: Fall Break''
  | <center>-</center>
+
||<center>-</center>
 +
||<center>-</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.10.11 Wed </center>
+
 
  | *''Sampling Methods for Large Simulations''
+
| <center>2023.10.11 Wed </center>
 +
||
 +
*''Sampling Methods for Large Simulations''
 
:1. Monte Carlo (MC)
 
:1. Monte Carlo (MC)
 
*''Predicting Protein Structure''  
 
*''Predicting Protein Structure''  
:2. Ab initio structure prediction (protein-folding)
+
:2. Ab initio structure prediction (protein-folding)  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.pdf  pdf]
Line 279: Line 333:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Luke001.pdf Metropolis Monte Carlo Simulation Tutorial, LearningFromTheWeb.net, Accessed Oct 2008, Luke, B.]
+
 
 +
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Luke001.pdf Metropolis Monte Carlo Simulation Tutorial, LearningFromTheWeb.net, Accessed Oct 2008, Luke, B.]
  
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen007.pdf Jorgensen, W. L.; TiradoRives, J., Monte Carlo vs Molecular Dynamics for Conformational Sampling. ''J. Phys. Chem.'' '''1996''', ''100'',14508-14513]
 
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen007.pdf Jorgensen, W. L.; TiradoRives, J., Monte Carlo vs Molecular Dynamics for Conformational Sampling. ''J. Phys. Chem.'' '''1996''', ''100'',14508-14513]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Dill001.pdf Dill, K. A.; Chan, H. S., From Levinthal to pathways to funnels. ''Nat. Struct. Biol.'' '''1997''', ''4'', 10-19]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Dill001.pdf Dill, K. A.; Chan, H. S., From Levinthal to pathways to funnels. ''Nat. Struct. Biol.'' '''1997''', ''4'', 10-19]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Metropolis001.pdf Metropolis, N.;et al., Equation of State Calculations by Fast Computing Machines. ''The Journal of Chemical Physics'' '''1953''', ''21'', 1087-1092]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Metropolis001.pdf Metropolis, N.;et al., Equation of State Calculations by Fast Computing Machines. ''The Journal of Chemical Physics'' '''1953''', ''21'', 1087-1092]
 
|-
 
|-
  | <center>2023.10.16 Mon </center>
+
 
  | *''Predicting Protein Structure''
+
| <center>2023.10.16 Mon </center>
:2. Example Trp-cage
+
||
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.mp4  S1 mp4]
+
*''Predicting Protein Structure''
 +
:1. Example Trp-cage
 +
:2. Comparative (homology) modeling
 +
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.pdf  pdf]
Line 296: Line 359:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Sali001.pdf Marti-Renom, M. A.; et al., Comparative protein structure modeling of genes and genomes. ''Annu. Rev. Biophys. Biomol. Struct.'' '''2000''',''29'',291-325]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Simmerling002.pdf Simmerling, C.;et al., All-atom structure prediction and folding simulations of a stable protein. ''J. Am. Chem. Soc.'' '''2002''', ''124'',11258-9]
  
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Simmerling002.pdf Simmerling, C.;et al., All-atom structure prediction and folding simulations of a stable protein. ''J. Am. Chem. Soc.'' '''2002''', ''124'',11258-9]
+
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Sali001.pdf Marti-Renom, M. A.; et al., Comparative protein structure modeling of genes and genomes. ''Annu. Rev. Biophys. Biomol. Struct.'' '''2000''',''29'',291-325]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Fersht001.pdf Daggett, V.; Fersht, A., The present view of the mechanism of protein folding. ''Nat. Rev. Mol. Cell Biol.'' '''2003''', ''4'', 497-502]
+
||
  
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Fersht001.pdf Daggett, V.; Fersht, A., The present view of the mechanism of protein folding. ''Nat. Rev. Mol. Cell Biol.'' '''2003''', ''4'', 497-502]
  
 +
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Sali002.pdf Fiser, A.; et al., Evolution and physics in comparative protein structure modeling. ''Acc. Chem. Res.'' '''2002''', ''35'', 413-21]
 
|-
 
|-
  | <center>2023.10.18 Wed</center>
+
 
  | *''Predicting Protein Structure''  
+
 
:1. Comparative (homology) modeling
+
 
:2. Neural Network
+
 
  | 1. No online presentation for paper #1
+
| <center>2023.10.18 Wed</center>
 +
||
 +
*''Predicting Protein Structure''  
 +
:1. Neural Network
 +
:2. Accelerated MD for Blind Protein Prediction
 +
||
 +
1. No online presentation for paper #1
 
<br>
 
<br>
  
Line 313: Line 386:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.18.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.18.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Hassabis001.pdf Senior, A.;et al, Improved protein structure prediction using potentials from deep learning. ''Nature'' '''2020''', ''577'', 1-5]
+
 
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Sali002.pdf Fiser, A.; et al., Evolution and physics in comparative protein structure modeling. ''Acc. Chem. Res.'' '''2002''', ''35'', 413-21]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Hassabis001.pdf Senior, A.;et al, Improved protein structure prediction using potentials from deep learning. ''Nature'' '''2020''', ''577'', 1-5]
 +
 
 +
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Dill002.pdf Perez, A.; et al., Blind protein structure prediction using accelerated free-energy simulations. ''Sci. Adv.'' '''2016''', ''2'']
 +
||
 +
 
 
|-
 
|-
  | <center>2023.10.23 Mon</center>
+
 
  | *''Predicting Protein Structure''
+
| <center>2023.10.23 Mon</center>
:1. Accelerated MD for Blind Protein Prediction
+
||
:2. Meso-Scale MD (Markov State Models)
+
*''Predicting Protein Structure''
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk01.mp4 S1 mp4 ]
+
:1. Meso-Scale MD (Markov State Models)  
 +
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk01.mp4 S1 mp4 ]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk01.pdf  pdf]
Line 328: Line 410:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk02.pdf  pdf ]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk02.pdf  pdf ]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Dill002.pdf Perez, A.; et al., Blind protein structure prediction using accelerated free-energy simulations. ''Sci. Adv.'' '''2016''', ''2'']
+
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Amaro001.pdf Durrant, J.;et al, Mesoscale All-Atom Influenza Virus Simulations Suggest New Substrate Binding Mechanism. ''ACS Central Science'' '''2020''', ''6'', 189-196]
+
||
  | 2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Pande002.pdf Husic, B.; et al., Markov State Models: From an Art to a Science. ''JACS'' '''2018''', ''140'', 2386-2396]
+
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Amaro001.pdf Durrant, J.;et al, Mesoscale All-Atom Influenza Virus Simulations Suggest New Substrate Binding Mechanism. ''ACS Central Science'' '''2020''', ''6'', 189-196]
 +
 
 +
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Pande002.pdf Husic, B.; et al., Markov State Models: From an Art to a Science. ''JACS'' '''2018''', ''140'', 2386-2396]
 +
 
 
|-
 
|-
  | <center>-</center>
+
 
  | <center>-</center>
+
|- style="background:lightgreen"
  | <center>-</center>
+
| <center>-</center>
  | <center>'''IN CLASS QUIZ for Section 3 2023.10.25 WED'''</center>
+
||<center>-</center>
  | <center>-</center>
+
||<center>-</center>
 +
||<center>'''IN CLASS QUIZ for Section 3 2023.10.25 WED'''</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.10.25 Wed </center>
+
 
  | '''SECTION IV: LEAD DISCOVERY'''
+
| <center>2023.10.25 Wed </center>
 +
||
 +
'''SECTION IV: LEAD DISCOVERY'''
 
*''Docking''
 
*''Docking''
 
:1. Introduction to DOCK
 
:1. Introduction to DOCK
:2. Test Sets (database enrichment)
+
:2. Test Sets (database enrichment)  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.pdf  pdf]
Line 350: Line 444:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo035.pdf Allen, W. J.; et al., DOCK 6: Impact of New Features and Current Docking Performance. ''Journal of computational chemistry'' '''2015''', ''36'', 1132-1156.]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo035.pdf Allen, W. J.; et al., DOCK 6: Impact of New Features and Current Docking Performance. ''Journal of computational chemistry'' '''2015''', ''36'', 1132-1156.]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shoichet003.pdf Mysinger, M.; et al., Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking. ''Journal of medicinal chemistry'' '''2012''', ''55'', 6582-94]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shoichet003.pdf Mysinger, M.; et al., Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking. ''Journal of medicinal chemistry'' '''2012''', ''55'', 6582-94]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kuntz002.pdf Ewing, T. J.; et al., DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases. ''J. Comput. Aided Mol. Des.'' '''2001''', ''15'', 411-28]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kuntz002.pdf Ewing, T. J.; et al., DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases. ''J. Comput. Aided Mol. Des.'' '''2001''', ''15'', 411-28]
 +
 
 
|-
 
|-
  | <center>2023.10.30 Mon</center>
+
 
  | *''Docking''  
+
| <center>2023.10.30 Mon</center>
 +
||
 +
*''Docking''  
 
:1. Test Sets (virtual screening)
 
:1. Test Sets (virtual screening)
 
:2. Footprint-based scoring
 
:2. Footprint-based scoring
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.mp4 S1 mp4]  
+
 
 +
||
 +
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.mp4 S1 mp4]  
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.pdf  pdf]  
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.pdf  pdf]  
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2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk02.mp4 S2 mp4]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk02.mp4 S2 mp4]
 
<br>
 
<br>
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk02.pdf  pdf]]
+
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shoichet001.pdf Irwin, J. J.; Shoichet, B. K., ZINC--a free database of commercially available compounds for virtual screening. ''J. Chem. Inf. Model.'' '''2005''', ''45'', 177-82]
+
||
 +
 
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shoichet001.pdf Irwin, J. J.; Shoichet, B. K., ZINC--a free database of commercially available compounds for virtual screening. ''J. Chem. Inf. Model.'' '''2005''', ''45'', 177-82]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo022.pdf Balius, T.E.; et al., Implementation and Evaluation of a Docking-Rescoring Method Using Molecular Footprint Comparisons. ''J. Comput. Chem.'' '''2011''', ''32'', 2273-2289.]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo022.pdf Balius, T.E.; et al., Implementation and Evaluation of a Docking-Rescoring Method Using Molecular Footprint Comparisons. ''J. Comput. Chem.'' '''2011''', ''32'', 2273-2289.]
  | 1. [https://zinc.docking.org ZINC Website at UCSF, Shoichet group]
+
 
 +
||
 +
 
 +
1. [https://zinc.docking.org ZINC Website at UCSF, Shoichet group]
 
|-
 
|-
  | <center>2023.11.01 Wed</center>
+
 
  | *''Discovery Methods''  
+
| <center>2023.11.01 Wed</center>
:2. Hotspot probes (GRID)
+
||
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk01.mp4 S1 mp4]
+
 
 +
 
 +
*''Discovery Methods''  
 +
:2. Hotspot probes (GRID)  
 +
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk02.pdf  pdf]
  | 2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Goodford001.pdf Goodford, P. J., A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. ''J. Med. Chem.'' '''1985''', ''28'', 849-57]
+
 
  |  
+
||
 +
 
 +
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Goodford001.pdf Goodford, P. J., A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. ''J. Med. Chem.'' '''1985''', ''28'', 849-57]
 +
||
 
|-
 
|-
  | <center>2023.11.06 Mon</center>
+
 
  | *''Discovery Methods''  
+
<center>-</center>
 +
|-
 +
 
 +
| <center>2023.11.06 Mon</center>
 +
||
 +
*''Discovery Methods''  
 
:1. COMFA
 
:1. COMFA
 
:2 Pharmacophores
 
:2 Pharmacophores
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kubinyi002.pdf Kubinyi, H., Comparative molecular field analysis (CoMFA). ''Encyclopedia of Computational Chemistry, Databases and Expert Systems Section'', John Wiley & Sons, Ltd. '''1998''']
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kubinyi002.pdf Kubinyi, H., Comparative molecular field analysis (CoMFA). ''Encyclopedia of Computational Chemistry, Databases and Expert Systems Section'', John Wiley & Sons, Ltd. '''1998''']
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Swaan001.pdf Chang, C.; et al., Pharmacophore-based discovery of ligands for drug transporters. ''Advanced Drug Delivery Reviews'' '''2006''', ''58'', 1431-1450]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Swaan001.pdf Chang, C.; et al., Pharmacophore-based discovery of ligands for drug transporters. ''Advanced Drug Delivery Reviews'' '''2006''', ''58'', 1431-1450]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Bunce001.pdf Cramer, R. D.; Patterson, D. E.; Bunce, J. D., Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. ''J. Am. Chem. Soc.'', ''1988'', ''110'', 5959-5967]
+
 
 +
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Bunce001.pdf Cramer, R. D.; Patterson, D. E.; Bunce, J. D., Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. ''J. Am. Chem. Soc.'', ''1988'', ''110'', 5959-5967]
 
|-
 
|-
  | <center>2023.11.08 Wed</center>
+
 
  | *''Discovery Methods.''  
+
| <center>2023.11.08 Wed</center>
 +
||
 +
*''Discovery Methods.''  
 
:1. Pharmacophores
 
:1. Pharmacophores
:2. De novo design
+
:2. De novo design  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Alvarez001.pdf Alvarez, J.; et al., Pharmacophore-Based Molecular Docking to Account for Ligand Flexibility. ''Proteins'' '''2003''', ''51'', 172-188 ]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Alvarez001.pdf Alvarez, J.; et al., Pharmacophore-Based Molecular Docking to Account for Ligand Flexibility. ''Proteins'' '''2003''', ''51'', 172-188 ]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shakhnovich001.pdf Cheron, N.; et al., OpenGrowth: An Automated and Rational Algorithm for Finding New Protein Ligands. ''J. Med. Chem.'' '''2016''', ''59'', 4171-4188]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shakhnovich001.pdf Cheron, N.; et al., OpenGrowth: An Automated and Rational Algorithm for Finding New Protein Ligands. ''J. Med. Chem.'' '''2016''', ''59'', 4171-4188]
  | <center>-</center>
+
||<center>-</center>
 
|-
 
|-
  | <center>2023.11.13 Mon</center>
+
 
  | *''Discovery Methods''  
+
| <center>2023.11.13 Mon</center>
 +
||
 +
*''Discovery Methods''  
 
:1. De novo design
 
:1. De novo design
:2. Genetic Algorithm
+
:2. Genetic Algorithm  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen016.pdf Jorgensen, W.; et al., Efficient drug lead discovery and optimization. ''Acc. of Chem. Research'' '''2009''', ''42 (6)'', 724-733]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen016.pdf Jorgensen, W.; et al., Efficient drug lead discovery and optimization. ''Acc. of Chem. Research'' '''2009''', ''42 (6)'', 724-733]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Pegg001.pdf Pegg, S. C.; Haresco, J. J.; Kuntz, I. D., A genetic algorithm for structure-based de novo design. ''J Comput Aided Mol Des'' '''2001''', ''15'', 911-33]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Pegg001.pdf Pegg, S. C.; Haresco, J. J.; Kuntz, I. D., A genetic algorithm for structure-based de novo design. ''J Comput Aided Mol Des'' '''2001''', ''15'', 911-33]
  | <center>-</center>
+
||<center>-</center>
 
|-
 
|-
  | <center>-</center>
+
 
  | <center>-</center>
+
|- style="background:lightgreen"
  | <center>-</center>
+
| <center>-</center>
  | <center>'''IN CLASS QUIZ for Section 4 2023.11.15 WED'''</center>
+
||<center>-</center>
  | <center>-</center>
+
||<center>-</center>
 +
||<center>'''IN CLASS QUIZ for Section 4 2023.11.15 WED'''</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.11.15 Wed</center>
+
 
  | '''SECTION V: LEAD REFINEMENT
+
| <center>2023.11.15 Wed</center>
 +
||
 +
'''SECTION V: LEAD REFINEMENT
 
*''Free Energy Methods''
 
*''Free Energy Methods''
 
:1. Thermolysin with two ligands (FEP)
 
:1. Thermolysin with two ligands (FEP)
 
:2. Fatty acid synthase I ligands (TI)
 
:2. Fatty acid synthase I ligands (TI)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.mp4  S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.pdf  pdf]
Line 450: Line 598:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman009.pdf Bash, P. A.; Singh, U. C.; Brown, F. K.; Langridge, R.; Kollman, P. A., Calculation of the relative change in binding free energy of a protein-inhibitor complex. ''Science'' '''1987''', ''235'', 574-6]
+
 
 +
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman009.pdf Bash, P. A.; Singh, U. C.; Brown, F. K.; Langridge, R.; Kollman, P. A., Calculation of the relative change in binding free energy of a protein-inhibitor complex. ''Science'' '''1987''', ''235'', 574-6]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/labahn001.pdf Labahn, A.; et al., Free energy calculations on the binding of novel thiolactomycin derivatives to E. coli fatty acid synthase I. ''Bioorg Med Chem.'' '''2012''', ''20'', 3446-53]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/labahn001.pdf Labahn, A.; et al., Free energy calculations on the binding of novel thiolactomycin derivatives to E. coli fatty acid synthase I. ''Bioorg Med Chem.'' '''2012''', ''20'', 3446-53]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/tronrud002.pdf Tronrud, D.E.; Holden, H.M.; Matthews, B.W.; Structures of Two Thermolysin-Inhibitor Complexes That Differ by a Single Hydrogen Bond. ''Science'' '''1987''', ''235'', 571-573]
+
 
 +
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/tronrud002.pdf Tronrud, D.E.; Holden, H.M.; Matthews, B.W.; Structures of Two Thermolysin-Inhibitor Complexes That Differ by a Single Hydrogen Bond. ''Science'' '''1987''', ''235'', 571-573]
  
 
1&2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen006.pdf Jorgensen, W. L., Free Energy Calculations:  A Breakthrough for Modeling Organic Chemistry in Solution. ''Accounts Chem. Res.'' '''1989''', ''22'', 184-189]
 
1&2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen006.pdf Jorgensen, W. L., Free Energy Calculations:  A Breakthrough for Modeling Organic Chemistry in Solution. ''Accounts Chem. Res.'' '''1989''', ''22'', 184-189]
Line 461: Line 614:
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lawrenz001.pdf Lawrenz, M.; et al., Independent-Trajectories Thermodynamic-Integration Free-Energy Changes for Biomolecular Systems: Determinants of H5N1 Avian Influenza Virus Neuraminidase Inhibition by Peramivir. ''J. Chem. Theory Comput.'' '''2009''', ''5'', 1106-1116]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lawrenz001.pdf Lawrenz, M.; et al., Independent-Trajectories Thermodynamic-Integration Free-Energy Changes for Biomolecular Systems: Determinants of H5N1 Avian Influenza Virus Neuraminidase Inhibition by Peramivir. ''J. Chem. Theory Comput.'' '''2009''', ''5'', 1106-1116]
 
|-
 
|-
  | <center>2023.11.20 Mon</center>
+
 
  | *'' MM-PB/GBSA''
+
| <center>2023.11.20 Mon</center>
 +
||
 +
 
 +
*'' MM-PB/GBSA''
 
:1. Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods
 
:1. Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods
 
*''MM-GBSA case studies''
 
*''MM-GBSA case studies''
 
:2. EGFR and mutants
 
:2. EGFR and mutants
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.mp4  S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.pdf  pdf]
Line 473: Line 631:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman012.pdf Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S. H.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. ''Accounts Chem. Res.'' '''2000''', ''33'', 889-897]
+
||
 +
 
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman012.pdf Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S. H.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. ''Accounts Chem. Res.'' '''2000''', ''33'', 889-897]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo019.pdf Balius, T.E.; Rizzo, R. C. Quantitative Prediction of Fold Resistance for Inhibitors of EGFR. ''Biochemistry'', '''2009''', ''48'', 8435-8448]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo019.pdf Balius, T.E.; Rizzo, R. C. Quantitative Prediction of Fold Resistance for Inhibitors of EGFR. ''Biochemistry'', '''2009''', ''48'', 8435-8448]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/bartlett000.pdf Bartlett, P. A.;  Marlowe, C. K., Evaluation of Intrinsic Binding Energy from a Hydrogen Bonding Group in an Enzyme Inhibitor. ''Science.'' '''1987''', ''235'',  569-571]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/bartlett000.pdf Bartlett, P. A.;  Marlowe, C. K., Evaluation of Intrinsic Binding Energy from a Hydrogen Bonding Group in an Enzyme Inhibitor. ''Science.'' '''1987''', ''235'',  569-571]
 +
 
 
|-
 
|-
  | <center>2021.11.22 Wed</center>
+
|- style="background:peachpuff"
  | *''No Class: Thanksgiving''
+
| <center>2021.11.22 Wed</center>
  | <center>-</center>
+
||
  | <center>-</center>
+
*''No Class: Thanksgiving''
  | <center>-</center>
+
||<center>-</center>
 +
||<center>-</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.11.27 Mon </center>
+
|-
  | *''MM-GBSA case studies''
+
 
 +
| <center>2023.11.27 Mon </center>
 +
||
 +
*''MM-GBSA case studies''
 
:1. ErbB family selectivity  
 
:1. ErbB family selectivity  
 
*''Linear Response''  
 
*''Linear Response''  
:2. Intro to Linear Response (LR method)
+
:2. Intro to Linear Response (LR method)  
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.mp4 S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.mp4 S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo024.pdf Huang, Y.; Rizzo, R. C. A Water-based Mechanism of Specificity and Resistance for Lapatinib with ErbB Family Kinases, ''Biochemistry'', '''2012''', ''51'', 2390-2406]
+
 
 +
||
 +
 
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo024.pdf Huang, Y.; Rizzo, R. C. A Water-based Mechanism of Specificity and Resistance for Lapatinib with ErbB Family Kinases, ''Biochemistry'', '''2012''', ''51'', 2390-2406]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Aqvist001.pdf Aqvist, J.; Mowbray, S. L., Sugar recognition by a glucose/galactose receptor. Evaluation of binding energetics from molecular dynamics simulations. ''J Biol Chem'' '''1995''', ''270'', 9978-81]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Aqvist001.pdf Aqvist, J.; Mowbray, S. L., Sugar recognition by a glucose/galactose receptor. Evaluation of binding energetics from molecular dynamics simulations. ''J Biol Chem'' '''1995''', ''270'', 9978-81]
  | <center>-</center>
+
 
 +
||<center>-</center>
 
|-
 
|-
  | <center>2023.11.29 Wed </center>
+
 
  | *''Linear Response''  
+
| <center>2023.11.29 Wed </center>
 +
||
 +
*''Linear Response''  
 
:1. Inhibition of protein kinases (Extended LR method)  
 
:1. Inhibition of protein kinases (Extended LR method)  
 
*''Properties of Known Drugs''
 
*''Properties of Known Drugs''
 
:2. Molecular Scaffolds (frameworks) and functionality (side-chains)
 
:2. Molecular Scaffolds (frameworks) and functionality (side-chains)
  | 1. No online presentation for paper #1
+
||
 +
 
 +
1. No online presentation for paper #1
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.mp4  S1 mp4]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen001.pdf Tominaga, Y.; Jorgensen, W. L.; General model for estimation of the inhibition of protein kinases using Monte Carlo simulations. ''J. Med. Chem.'' '''2004''', ''47'', 2534-2549]
+
||
 +
 
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Jorgensen001.pdf Tominaga, Y.; Jorgensen, W. L.; General model for estimation of the inhibition of protein kinases using Monte Carlo simulations. ''J. Med. Chem.'' '''2004''', ''47'', 2534-2549]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Murcko001.pdf Bemis, G. W.; Murcko, M. A., The properties of known drugs. 1. Molecular frameworks. ''J. Med. Chem.'' '''1996''', ''39'', 2887-93]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Murcko001.pdf Bemis, G. W.; Murcko, M. A., The properties of known drugs. 1. Molecular frameworks. ''J. Med. Chem.'' '''1996''', ''39'', 2887-93]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Murcko002.pdf Bemis, G. W.; Murcko, M. A., Properties of known drugs. 2. Side chains. ''J. Med. Chem.'' '''1999''', ''42'', 5095-9]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Murcko002.pdf Bemis, G. W.; Murcko, M. A., Properties of known drugs. 2. Side chains. ''J. Med. Chem.'' '''1999''', ''42'', 5095-9]
  | <center>-</center>
+
||<center>-</center>
 
|-
 
|-
  | <center>2023.12.04 Mon </center>
+
 
  | *''Properties of Known Drugs''
+
| <center>2023.12.04 Mon </center>
 +
||
 +
*''Properties of Known Drugs''
 
:1. Lipinski Rule of Five
 
:1. Lipinski Rule of Five
 
:2 ADME Prediction
 
:2 ADME Prediction
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.mp4  S1 mp4]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.pdf  pdf]
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<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lipinski002.pdf Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. ''Adv. Drug. Deliv. Rev.'' '''2001''', ''46'', 3-26]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lipinski002.pdf Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. ''Adv. Drug. Deliv. Rev.'' '''2001''', ''46'', 3-26]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Xu001.pdf Hou, T. J.; Xu, X. J.; ADME evaluation in drug discovery. ''J. Mol. Model'', '''2002''', ''8'', 337-349]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Xu001.pdf Hou, T. J.; Xu, X. J.; ADME evaluation in drug discovery. ''J. Mol. Model'', '''2002''', ''8'', 337-349]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lipinski001.pdf Lipinski, C. A., Chris Lipinski discusses life and chemistry after the Rule of Five. ''Drug. Discov. Today'' '''2003''', ''8'', 12-6]
+
||
 +
 
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lipinski001.pdf Lipinski, C. A., Chris Lipinski discusses life and chemistry after the Rule of Five. ''Drug. Discov. Today'' '''2003''', ''8'', 12-6]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Xu003.pdf Hou, T. J.; Xu, X. J.; AMDE Evaluation in drug discovery 3. Modeling blood-brain barrier partitioning using simple molecular descriptors. ''J. Chem. Inf. Comput. Sci.'', '''2003''', ''43'', 2137-2152]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Xu003.pdf Hou, T. J.; Xu, X. J.; AMDE Evaluation in drug discovery 3. Modeling blood-brain barrier partitioning using simple molecular descriptors. ''J. Chem. Inf. Comput. Sci.'', '''2003''', ''43'', 2137-2152]
 
|-
 
|-
  | <center>2023.12.06 Wed </center>
+
|-
  | *''Properties of Known Drugs''
+
 
 +
| <center>2023.12.06 Wed </center>
 +
||
 +
*''Properties of Known Drugs''
 
:1. Synthetic Accessibility
 
:1. Synthetic Accessibility
 
:2. QED
 
:2. QED
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.mp4  S1 mp4]
+
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.pdf  pdf]
Line 547: Line 742:
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk02.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk02.pdf  pdf]
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Ertl2009.pdf Ertl, P.; Schuffenhauer, A.; Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. ''J. Cheminformatics'', '''2009''', ''1'', 8]
+
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Ertl2009.pdf Ertl, P.; Schuffenhauer, A.; Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. ''J. Cheminformatics'', '''2009''', ''1'', 8]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Bickerton2012.pdf Bickerton, G. R., Quantifying the chemical beauty of drugs. ''Nature Chemistry'' '''2012''', ''4'', 90-98]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Bickerton2012.pdf Bickerton, G. R., Quantifying the chemical beauty of drugs. ''Nature Chemistry'' '''2012''', ''4'', 90-98]
  | <center>-</center>
+
||<center>-</center>
 
|-
 
|-
  | <center>2023.12.11 Mon </center>
+
 
  | *''From Target to Market''
+
| <center>2023.12.11 Mon </center>
 +
||
 +
*''From Target to Market''
 
:1. Drug Discovery Overview
 
:1. Drug Discovery Overview
 
:2. Attrition Rates
 
:2. Attrition Rates
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.mp4  S1 mp4]
+
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.mp4  S1 mp4]
 
<br>
 
<br>
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.pdf  pdf]
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.pdf  pdf]
  
 
2. No online presentation for paper #2
 
2. No online presentation for paper #2
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Philpott001.pdf Hughes, J.;  et. al., Principles of early drug discovery. ''British journal of pharmacology'' '''2010''', ''162'', 1239-49.]
+
||
 +
1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Philpott001.pdf Hughes, J.;  et. al., Principles of early drug discovery. ''British journal of pharmacology'' '''2010''', ''162'', 1239-49.]
  
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Weir001.pdf Waring, M.; et. al., An analysis of the attrition of drug candidates from four major pharmaceutical companies ''Nature reviews'' '''2015''', ''14''.]
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Weir001.pdf Waring, M.; et. al., An analysis of the attrition of drug candidates from four major pharmaceutical companies ''Nature reviews'' '''2015''', ''14''.]
  | <center>
+
||<center>
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/ClinicalTrials.pdf Understanding Clinical Trial Terminology: What's a Phase 1, 2 OR 3 Clinical Trial?. ''www.concertpharma.com'', '''2019''']
 
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/ClinicalTrials.pdf Understanding Clinical Trial Terminology: What's a Phase 1, 2 OR 3 Clinical Trial?. ''www.concertpharma.com'', '''2019''']
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020.11.30.ams535_thermo_cycles_study_guide.pdf Thermodynamic Cycles]  
 
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020.11.30.ams535_thermo_cycles_study_guide.pdf Thermodynamic Cycles]  
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</center>
 
</center>
 
|-
 
|-
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  | <center>-</center>
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|- style="background:lightgreen"
  | <center>-</center>
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| <center>-</center>
  | <center>'''IN CLASS QUIZ for Section 5 2023.12.11 WED'''</center>
+
||<center>-</center>
  | <center>-</center>
+
||<center>-</center>
 +
||<center>'''IN CLASS QUIZ for Section 5 2023.12.11 WED'''</center>
 +
||<center>-</center>
 
|-
 
|-
  | <center>-</center>
+
 
  | *'''''Final Exam'''''
+
|<center>-</center>
  | <center>-</center>
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||
  | No Final Exam in AMS-535/CHE-535 for Fall 2023
+
*'''''Final Exam'''''  
  | <center>-</center>
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||<center>-</center>
 +
||No Final Exam in AMS-535/CHE-535 for Fall 2023
 +
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|-
 
|-
 
|}
 
|}

Revision as of 11:53, 6 September 2023


Please see https://ringo.ams.stonybrook.edu/~rizzo for Rizzo Group Homepage


Instructors Dr. Robert C. Rizzo [631-632-8519, rizzorc -at- gmail.com]

Steven Pak [631-632-8519, steven dot pak -at- stonybrook dot edu]

John Bickel [631-632-8519, john dot bickel -at- stonybrook dot edu]

Course No. AMS-535 / CHE-535
Location/Time Mathematics S235S, Monday and Wednesday 2:30PM - 3:50PM
Office Hours Anytime by appointment, Math Tower 3-129
Grading Grades will be based on the quality of:

(1) Pre-recorded oral presentations (25%)

Student will pre-record 1-2 ZOOM presentations based on papers assigned from the schedule below which will be uploaded to the class wiki for viewing by class participants

(2) Class discussion (30%)

At scheduled class times, students will attend class in-person and discuss the papers they have read and the presentations they have watched. For each paper, each student will prepare 2 thoughtful questions ahead of time to facilitate scientific discussion. Copies of these questions will be handed to the instructors prior to the beginning of discussion.

(3) In-class quizzes (45%)

Five in class quizzes will be assigned based on the 5 major sections of the course and the lowest quiz grade will be dropped.


GENERAL INFORMATION: AMS-535 provides an introduction to the field of computational structure-based drug design. The course aims to foster collaborative learning and will consist of presentations by instructors, course participants, and guest lecturers arranged in five major sections outlined below. Presentations should aim to summarize key papers, theory, and application of computational methods relevant to computational drug design. Grade will be based on oral presentations, class discussion/attendance/participation, and quizzes.


Learning Objectives

  • (1) Become informed about the field of computational structure-based drug design and the pros and cons of its methods.
  • (2) Dissect seminal theory and application papers relevant to computational drug design.
  • (3) Gain practice in giving an in-depth oral powerpoint presentation on computational drug design.
  • (4) Read, participate in discussion, and be tested across five key subject areas:
    • (i) Drug Discovery and Biomolecular Structure:
      Drug Discovery, Chemistry Review, Proteins, Carbohydrates, Nucleic acids
      Molecular Interactions and Recognition, Experimental Techniques for Elucidating Structure
    • (ii) Molecular Modeling:
      Classical Force Fields (Molecular Mechanics),
      Solvent Models, Condensed-phase Calculations, Parameter Development
    • (iii) Sampling Methods:
      Conformational Space, Molecular Dynamics (MD), Metropolis Monte Carlo (MC)
      Sampling Techniques, Predicting Protein Structure, Protein Folding
    • (iv) Lead Discovery:
      Docking as a Lead Generation Tool, Docking Algorithms
      Discovery Methods I, Discovery Methods II, Applications
    • (v) Lead Refinement:
      Free Energy Perturbation (FEP), Linear Response (LR), Extended Linear Response (ELR)
      MM-PBSA, MM-GBSA, Properties of Known Drugs, Property Prediction


LITERATURE DISCLAIMER: Hyperlinks and manuscripts accessed through Stony Brook University's electronic journal subscriptions are provided below for educational purposes only.


PRESENTATION DISCLAIMER: Presentations may contain slides from a variety of online sources for educational and illustrative purposes only, and use here does not imply that the presenter is claiming that the contents are their own original work or research.

Syllabus Notes

This is a mixed course meaning that there will be both synchronous and asynchronous aspects. Note that course grading criteria has been modified from previous years (see grading breakdown above). Other details for this semester are as follows:

General Information:

  • We will hold class at the regularly scheduled time (M/W 2:30-3:50PM) and class will be held in person. There is no online section.
  • The first 5 lectures are to help put everyone on an even footing with regards to background material and will be given by the Instructors at the regularly scheduled class time.
  • All class correspondence should be addressed to ALL course Instructors.

Discussion Sessions:

  • The bulk of the classes will be devoted to in-person discussion, in breakout groups, facilitated by an assigned discussion leader. Papers will be read prior to meeting (1-2 per class) for which everyone will also have watched an oral presentation on the paper (1-2 per class). Oral presentations will be in the form of pre-recorded videos made by students taking the class.
  • For each paper discussed, one (1) student in each discussion group will be assigned as discussion leader. The discussion group leader will be expected to understand and guide discussion on the paper. If there is any confusion regarding paper content as a discussion leader, students should reach out to TAs well before the class in which they are to lead.
  • The Instructors(s) will moderate and participate in discussion, as well as field questions and clear up any misunderstandings, and take over discussion when necessary.
  • For each paper, each student will prepare 2 thoughtful questions ahead of time to facilitate scientific discussion. Copies of these questions will be handed to the instructors prior to the beginning of discussion.
  • A sizeable portion of the class grade (30%) is based on these discussion sections. Thus, it is important that everyone attend all of the classes and participate in each discussion to receive full credit.
  • If a student is unable to attend a specific class for reasons beyond their control they will instead be asked to email the instructor(s) AND submit a one page Paper Summary Sheet answering questions about the papers that were discussed on the day that they missed. The "Paper Summary Sheets" will form the basis of the "Discussion" part of their grade for any synchronous classes that were missed.
  • If a student misses a class they will have 24 hours to submit their Paper Summary Sheets. Late Paper Summary Sheets will not be accepted.

Oral Presentations:

  • Students will pre-record 1-2 ZOOM presentations based on papers assigned to them from the schedule shown below.
  • Students will email their pre-recorded presentations to ALL course Instructors by Friday at 5PM before the week in which their presentations will be discussed.
  • Course participants will watch the student presentations and, independently, read the paper before the class in which they are to be discussed.
  • Course participants will score each student presentation using a Presentation Assessment Sheet which will be emailed to ALL Instructors within 24 hours after the class in which the presentation was discussed.

In-class Quizzes:

  • Five quizzes will be used to assess student understanding of the course material.
  • The quiz format is in-class, closed book.
  • Answers to quiz questions should integrate topics, concepts, and outcomes of the different papers covered for the section being tested.
  • Students are expected to work alone and do their own work. Representing another person's work as your own is always wrong. The Instructors are required to report any suspected instances of academic dishonesty to the Academic Judiciary.

Recording Your Oral Presentations Using Zoom: It is very straightforward to create a video of yourself giving a PPT presentation using Zoom:

  • Download the Zoom app ( https://it.stonybrook.edu/services/zoom )
  • Open the Zoom app
  • Create a new Zoom meeting with only yourself (make sure audio and video are turned on)
  • Share your screen
  • Open your paper presentation in PPT and put in presentation mode
  • Start recording and give a short test presentation to make sure that everything is working smoothly (use mouse as necessary to highlight specific regions of your slides)
  • Stop recording and quit the meeting
  • Open the newly created video (using QuickTime or some other video player) to make sure that your test presentation has both audio and video and looks good
  • Follow the above steps to create your "full-length" video presentation (videos should not exceed 20-25 minutes)
  • Email your video to ALL Instructors who will make it available to the class (please name your Zoom video Lastname_Paper1.mp4 or Lastname_Paper2.mp4 )

Oral Presentation Guidelines: Pre-recorded talks should be formal (as if at a scientific meeting or job talk), presented in PPT format, and be 20-25 minutes long. All talks will be posted on the course website. References should occur at the bottom of each slide when necessary. Presentations should be based mostly on the primary references however secondary references and other sources may be required to make some presentations complete. It is the responsibility of each presenter to email their talk by Friday at 5PM before the week in which their talk is being discussed. Talks will likely be arranged in the following order:

  • Introduction/Background (include biological relevance if applicable)
  • Specifics of the System or General Problem
  • Computational Methods (theory) and Details (system setup) being used
  • Results and Discussion (critical interpretation of results and any problems/challenges)
  • Conclusions/Future
  • Acknowledgments



Class Schedule

-


-


Date
Topic
Speaker and Presentation
Primary Reference
Secondary Reference
2023.08.28 Mon
  • Organizational Meeting
Rizzo, R. mp4 Course introduction and format. Go over Syllabus. Course participant background and introductions.
-
2023.08.30 Wed

SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE

  • Drug Discovery
  1. Introduction, history, irrational vs. rational
  2. Viral Target Examples

Rizzo, R. mp4

Rizzo, R. pdf pdf_handout

1. Jorgensen, W.L., The many roles of computation in drug discovery. Science 2004, 303, 1813-8

2. Kuntz, I. D., Structure-based strategies for drug design and discovery. Science 1992, 257, 1078-1082

-
2023.09.04 Mon
  • No Class: Labor Day
-
-
-
2023.09.06 Wed
  • Chemistry Review
  1. Molecular structure, bonding, graphical representations
  2. Functionality, properties of organic molecules

Rizzo, R. mp4

Rizzo, R. pdf

in class lecture
-
2023.09.11 Mon
  • Biomolecular Structure
1. Lipids, carbohydrates
2. Nucleic acids, proteins

Rizzo, R. mp4

Rizzo, R. pdf

in class lecture
structures of the 20 amino acid side chains
2023.09.13 Wed
  • Molecular Interactions and Recognition
1. Electrostatics, VDW interactions, hydrophobic effect, molecular recognition (binding energy)
2. Inhibitors types: allosteric, transition state, covalent vs non-covalent, selective, competitive

Rizzo, R. mp4

Rizzo, R. pdf

in class lecture
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2023.09.18 Mon
  • Intro. to Methods in 3-D Structure Determination
1. Crystallography, NMR
2. Structure Quality, PDB in detail

Rizzo, R. mp4

Rizzo, R. pdf

in class lecture
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IN CLASS QUIZ for Section 1 2023.09.20 WED
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2023.09.20 Wed
QUIZ #1 FIRST 30 MINUTES

SECTION II: MOLECULAR MODELING

  • Classical Force Fields
1. All-atom Molecular Mechanics
1. Alseika, Zachary mp4 pdf

1. Mackerell, A. D., Jr., Empirical force fields for biological macromolecules: overview and issues. J. Comput. Chem. 2004, 25, 1584-604

1. van Gunsteren, W. F.; et al., Biomolecular modeling: Goals, problems, perspectives. Angew. Chem. Int. Ed. Engl. 2006, 45, 4064-92

2023.09.25 Mon
  • Classical Force Fields
1. OPLS
2. AMBER
1. S1 mp4 pdf


2. S2 mp4 pdf

1. Jorgensen, W. L.; et al., Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236

2. Cornell, W. D.; et al., A Second Generation Force Field For the Simulation of Proteins, Nucleic Acids, and Organic Molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197

1. Jorgensen, W. L.; et al., The Opls Potential Functions For Proteins - Energy Minimizations For Crystals of Cyclic-Peptides and Crambin. J. Am. Chem. Soc. 1988, 110, 1657-1671

2. Bayly, C. I.; et al., A Well-Behaved Electrostatic Potential Based Method Using Charge Restraints For Deriving Atomic Charges - the RESP Model. J. Phys. Chem. 1993, 97, 10269-10280

2023.09.27 Wed
  • Explicit Solvent Models
1. Water models (TIP3P, TIP4P, SPC)
2. Condensed-phase calculations (DGhydration)
1. S1 mp4 pdf

2. S2 mp4 pdf

1. Jorgensen, W. L.; et al., Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 1983, 79, 926-935

2. Jorgensen, W. L.; et al., Monte Carlo Simulation of Differences in Free Energies of Hydration. J. Chem. Phys. 1985, 83, 3050-3054

2. Thermodynamic Cycle as Drawn By Dr. Rizzo
2023.10.02 Mon
  • Continuum Solvent Models
1. Generalized Born Surface Area (GBSA)
2. Poisson-Boltzmann Surface Area (PBSA)
1. S1 mp4 pdf

2. S2 mp4 pdf

1. Still, W. C.; et al., Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. J. Am. Chem. Soc 1990, 112, 6127-6129

2. Sitkoff, D.; et al., Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models. J. Phys. Chem. 1994, 98, 1978-1988

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IN CLASS QUIZ for Section 2 2023.10.04 WED
Additional resources:

1. Duarte Ramos Matos, G.; et al., Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database. J. Chem. Eng. Data 2017, 62, 1559-1569
2. Loeffler, H. H.; et al., Reproducibility of Free Energy Calculations across Different Molecular Simulation Software Packages J. Chem. Theory Comput. 2018, 14, 5567−5582

2023.10.04 Wed

SECTION III: SAMPLING METHODS

  • Molecular Conformations
1. Small molecules, peptides, relative energy, minimization methods
  • Sampling Methods for Large Simulations
2. Molecular dynamics (MD)

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Howard, A. E.; Kollman, P. A., An analysis of current methodologies for conformational searching of complex molecules. J. Med. Chem. 1988, 31, 1669-75

2. Karplus, M.; Petsko, G. A., Molecular dynamics simulations in biology. Nature 1990, 347, 631-9

1. Section 4 (PAGES 22-27) Colby College Molecular Mechanics Tutorial Introduction, 2004, Shattuck, T.W., Colby College

1. Holloway, M. K., A priori prediction of ligand affinity by energy minimization. Perspect. Drug Discov. Design 1998, 9-11, 63-84

2023.10.09 Mon
  • No Class: Fall Break
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2023.10.11 Wed
  • Sampling Methods for Large Simulations
1. Monte Carlo (MC)
  • Predicting Protein Structure
2. Ab initio structure prediction (protein-folding)

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Metropolis Monte Carlo Simulation Tutorial, LearningFromTheWeb.net, Accessed Oct 2008, Luke, B.

1. Jorgensen, W. L.; TiradoRives, J., Monte Carlo vs Molecular Dynamics for Conformational Sampling. J. Phys. Chem. 1996, 100,14508-14513

2. Dill, K. A.; Chan, H. S., From Levinthal to pathways to funnels. Nat. Struct. Biol. 1997, 4, 10-19

1. Metropolis, N.;et al., Equation of State Calculations by Fast Computing Machines. The Journal of Chemical Physics 1953, 21, 1087-1092

2023.10.16 Mon
  • Predicting Protein Structure
1. Example Trp-cage
2. Comparative (homology) modeling

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Simmerling, C.;et al., All-atom structure prediction and folding simulations of a stable protein. J. Am. Chem. Soc. 2002, 124,11258-9

2. Marti-Renom, M. A.; et al., Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 2000,29,291-325

1. Daggett, V.; Fersht, A., The present view of the mechanism of protein folding. Nat. Rev. Mol. Cell Biol. 2003, 4, 497-502

2. Fiser, A.; et al., Evolution and physics in comparative protein structure modeling. Acc. Chem. Res. 2002, 35, 413-21

2023.10.18 Wed
  • Predicting Protein Structure
1. Neural Network
2. Accelerated MD for Blind Protein Prediction

1. No online presentation for paper #1

2. S1 mp4
pdf

1. Senior, A.;et al, Improved protein structure prediction using potentials from deep learning. Nature 2020, 577, 1-5

2. Perez, A.; et al., Blind protein structure prediction using accelerated free-energy simulations. Sci. Adv. 2016, 2

2023.10.23 Mon
  • Predicting Protein Structure
1. Meso-Scale MD (Markov State Models)

1. S1 mp4
pdf


2. S2 mp4
pdf

1. Durrant, J.;et al, Mesoscale All-Atom Influenza Virus Simulations Suggest New Substrate Binding Mechanism. ACS Central Science 2020, 6, 189-196

1. Husic, B.; et al., Markov State Models: From an Art to a Science. JACS 2018, 140, 2386-2396

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IN CLASS QUIZ for Section 3 2023.10.25 WED
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2023.10.25 Wed

SECTION IV: LEAD DISCOVERY

  • Docking
1. Introduction to DOCK
2. Test Sets (database enrichment)

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Allen, W. J.; et al., DOCK 6: Impact of New Features and Current Docking Performance. Journal of computational chemistry 2015, 36, 1132-1156.

2. Mysinger, M.; et al., Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking. Journal of medicinal chemistry 2012, 55, 6582-94

1. Ewing, T. J.; et al., DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases. J. Comput. Aided Mol. Des. 2001, 15, 411-28

2023.10.30 Mon
  • Docking
1. Test Sets (virtual screening)
2. Footprint-based scoring

1. S1 mp4
pdf

2. S2 mp4
pdf


1. Irwin, J. J.; Shoichet, B. K., ZINC--a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005, 45, 177-82

2. Balius, T.E.; et al., Implementation and Evaluation of a Docking-Rescoring Method Using Molecular Footprint Comparisons. J. Comput. Chem. 2011, 32, 2273-2289.

1. ZINC Website at UCSF, Shoichet group

2023.11.01 Wed


  • Discovery Methods
2. Hotspot probes (GRID)

1. S1 mp4
pdf

2. S2 mp4
pdf

2. Goodford, P. J., A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J. Med. Chem. 1985, 28, 849-57

2023.11.06 Mon
  • Discovery Methods
1. COMFA
2 Pharmacophores

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Kubinyi, H., Comparative molecular field analysis (CoMFA). Encyclopedia of Computational Chemistry, Databases and Expert Systems Section, John Wiley & Sons, Ltd. 1998

2. Chang, C.; et al., Pharmacophore-based discovery of ligands for drug transporters. Advanced Drug Delivery Reviews 2006, 58, 1431-1450

1. Cramer, R. D.; Patterson, D. E.; Bunce, J. D., Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc., 1988, 110, 5959-5967

2023.11.08 Wed
  • Discovery Methods.
1. Pharmacophores
2. De novo design

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Alvarez, J.; et al., Pharmacophore-Based Molecular Docking to Account for Ligand Flexibility. Proteins 2003, 51, 172-188

2. Cheron, N.; et al., OpenGrowth: An Automated and Rational Algorithm for Finding New Protein Ligands. J. Med. Chem. 2016, 59, 4171-4188

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2023.11.13 Mon
  • Discovery Methods
1. De novo design
2. Genetic Algorithm

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Jorgensen, W.; et al., Efficient drug lead discovery and optimization. Acc. of Chem. Research 2009, 42 (6), 724-733

2. Pegg, S. C.; Haresco, J. J.; Kuntz, I. D., A genetic algorithm for structure-based de novo design. J Comput Aided Mol Des 2001, 15, 911-33

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IN CLASS QUIZ for Section 4 2023.11.15 WED
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2023.11.15 Wed

SECTION V: LEAD REFINEMENT

  • Free Energy Methods
1. Thermolysin with two ligands (FEP)
2. Fatty acid synthase I ligands (TI)

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Bash, P. A.; Singh, U. C.; Brown, F. K.; Langridge, R.; Kollman, P. A., Calculation of the relative change in binding free energy of a protein-inhibitor complex. Science 1987, 235, 574-6

2. Labahn, A.; et al., Free energy calculations on the binding of novel thiolactomycin derivatives to E. coli fatty acid synthase I. Bioorg Med Chem. 2012, 20, 3446-53

1. Tronrud, D.E.; Holden, H.M.; Matthews, B.W.; Structures of Two Thermolysin-Inhibitor Complexes That Differ by a Single Hydrogen Bond. Science 1987, 235, 571-573

1&2. Jorgensen, W. L., Free Energy Calculations: A Breakthrough for Modeling Organic Chemistry in Solution. Accounts Chem. Res. 1989, 22, 184-189

1&2. Kollman, P., Free Energy Calculations: Applications to Chemical and Biochemical Phenomena. Chem. Rev. 1993, 93, 2395-2417

2. Lawrenz, M.; et al., Independent-Trajectories Thermodynamic-Integration Free-Energy Changes for Biomolecular Systems: Determinants of H5N1 Avian Influenza Virus Neuraminidase Inhibition by Peramivir. J. Chem. Theory Comput. 2009, 5, 1106-1116

2023.11.20 Mon
  • MM-PB/GBSA
1. Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods
  • MM-GBSA case studies
2. EGFR and mutants

1. S1 mp4
pdf

2. S2 mp4
pdf


1. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S. H.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Accounts Chem. Res. 2000, 33, 889-897

2. Balius, T.E.; Rizzo, R. C. Quantitative Prediction of Fold Resistance for Inhibitors of EGFR. Biochemistry, 2009, 48, 8435-8448

1. Bartlett, P. A.; Marlowe, C. K., Evaluation of Intrinsic Binding Energy from a Hydrogen Bonding Group in an Enzyme Inhibitor. Science. 1987, 235, 569-571

2021.11.22 Wed
  • No Class: Thanksgiving
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2023.11.27 Mon
  • MM-GBSA case studies
1. ErbB family selectivity
  • Linear Response
2. Intro to Linear Response (LR method)

1. S1 mp4
pdf

2. S2 mp4
pdf


1. Huang, Y.; Rizzo, R. C. A Water-based Mechanism of Specificity and Resistance for Lapatinib with ErbB Family Kinases, Biochemistry, 2012, 51, 2390-2406

2. Aqvist, J.; Mowbray, S. L., Sugar recognition by a glucose/galactose receptor. Evaluation of binding energetics from molecular dynamics simulations. J Biol Chem 1995, 270, 9978-81

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2023.11.29 Wed
  • Linear Response
1. Inhibition of protein kinases (Extended LR method)
  • Properties of Known Drugs
2. Molecular Scaffolds (frameworks) and functionality (side-chains)

1. No online presentation for paper #1

2. S1 mp4
pdf


1. Tominaga, Y.; Jorgensen, W. L.; General model for estimation of the inhibition of protein kinases using Monte Carlo simulations. J. Med. Chem. 2004, 47, 2534-2549

2. Bemis, G. W.; Murcko, M. A., The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 1996, 39, 2887-93

2. Bemis, G. W.; Murcko, M. A., Properties of known drugs. 2. Side chains. J. Med. Chem. 1999, 42, 5095-9

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2023.12.04 Mon
  • Properties of Known Drugs
1. Lipinski Rule of Five
2 ADME Prediction

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 2001, 46, 3-26

2. Hou, T. J.; Xu, X. J.; ADME evaluation in drug discovery. J. Mol. Model, 2002, 8, 337-349

1. Lipinski, C. A., Chris Lipinski discusses life and chemistry after the Rule of Five. Drug. Discov. Today 2003, 8, 12-6

2. Hou, T. J.; Xu, X. J.; AMDE Evaluation in drug discovery 3. Modeling blood-brain barrier partitioning using simple molecular descriptors. J. Chem. Inf. Comput. Sci., 2003, 43, 2137-2152

2023.12.06 Wed
  • Properties of Known Drugs
1. Synthetic Accessibility
2. QED

1. S1 mp4
pdf

2. S2 mp4
pdf

1. Ertl, P.; Schuffenhauer, A.; Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J. Cheminformatics, 2009, 1, 8

2. Bickerton, G. R., Quantifying the chemical beauty of drugs. Nature Chemistry 2012, 4, 90-98

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2023.12.11 Mon
  • From Target to Market
1. Drug Discovery Overview
2. Attrition Rates

1. S1 mp4
pdf

2. No online presentation for paper #2

1. Hughes, J.; et. al., Principles of early drug discovery. British journal of pharmacology 2010, 162, 1239-49.

2. Waring, M.; et. al., An analysis of the attrition of drug candidates from four major pharmaceutical companies Nature reviews 2015, 14.

2. Understanding Clinical Trial Terminology: What's a Phase 1, 2 OR 3 Clinical Trial?. www.concertpharma.com, 2019 Thermodynamic Cycles
Course Wrap-Up Topics

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IN CLASS QUIZ for Section 5 2023.12.11 WED
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  • Final Exam
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No Final Exam in AMS-535/CHE-535 for Fall 2023
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Required Syllabi Statements:

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