View source for 2023 AMS-535 Fall

__NOTOC__

=== <center> Please see https://ringo.ams.stonybrook.edu/~rizzo for Rizzo Group Homepage </center> ===
<br>
{| align="center" border="2" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:80%"
|- style="background:white"
! style="width:10%" | '''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: <br>

(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 <br>
(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.
|-
|}
<br>
'''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: <br />Drug Discovery, Chemistry Review, Proteins, Carbohydrates, Nucleic acids <br />Molecular Interactions and Recognition, Experimental Techniques for Elucidating Structure
**(ii) Molecular Modeling: <br />Classical Force Fields (Molecular Mechanics),  <br />Solvent Models, Condensed-phase Calculations, Parameter Development
**(iii) Sampling Methods: <br />Conformational Space, Molecular Dynamics (MD), Metropolis Monte Carlo (MC) <br />Sampling Techniques, Predicting Protein Structure, Protein Folding
**(iv) Lead Discovery:<br />Docking as a Lead Generation Tool, Docking Algorithms<br />Discovery Methods I, Discovery Methods II, Applications
**(v) Lead Refinement:<br />Free Energy Perturbation (FEP), Linear Response (LR), Extended Linear Response (ELR)<br />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 <b> will be expected </b> 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 <b> and participate in each discussion </b> 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  [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020_ams.che535.paper.summary.docx 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 [http://ringo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020_ams.che535.presentation.assessment.docx 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

<br>
<br>

== '''Class Schedule''' ==
{| align="center" border="1" cellpadding="8" cellspacing="0" style="background:white; text-align:left; width:95%"
|- style="background:cornflowerblue"
| <center>'''Date'''</center>
| <center>'''Topic'''</center>
| <center>'''Speaker and Presentation'''</center>
| <center>'''Primary Reference'''</center>
| <center>'''Secondary Reference'''</center>
|-

| <center>2023.08.28 Mon</center>
|| 
*''Organizational Meeting''
||[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>2023.08.30 Wed</center>
||
'''SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE'''
*''Drug Discovery''
# Introduction, history, irrational vs. rational
# Viral Target Examples

||
[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]

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>
|-

|- style="background:peachpuff"
| <center>2023.09.04 Mon</center>
|| 
*''No Class: Labor Day''
||<center>-</center>
||<center>-</center>
||<center>-</center>
|-
| <center>2023.09.06 Wed</center>
|| 
*''Chemistry Review''
# Molecular structure, bonding, graphical representations 
# Functionality, properties of organic molecules 

||
[http://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2022.08.29.ams535.rizzo.lect.002.pdf Rizzo, R. pdf]
|| <center>in class lecture</center>
|| <center>-</center>
|-

| <center>2023.09.11 Mon</center>
|| 
*''Biomolecular Structure''
:1. Lipids, carbohydrates 
:2. Nucleic acids, proteins  

||
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2022.08.31.ams535.rizzo.lect.003.mp4 Rizzo, R. mp4]
<br>
<br>
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2022.08.31.ams535.rizzo.lect.003.pdf Rizzo, R. pdf]
|| <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]
|-


| <center>2023.09.13 Wed</center>
|| 
*''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  
||
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2022.09.07.ams535.rizzo.lect.004.mp4 Rizzo, R. mp4]
<br>
<br>
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2022.09.07.ams535.rizzo.lect.004.pdf Rizzo, R. pdf]
|| <center>in class lecture</center>
|| <center>-</center>
|-

| <center>2023.09.18 Mon</center>
|| 
*''Intro. to Methods in 3-D Structure Determination''
:1. Crystallography, NMR 
: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]
<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]
|| <center>in class lecture</center>
|| <center>-</center>
|-

|- style="background:lightgreen"
| <center>-</center>
||<center>-</center>
||<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 
'''SECTION II: MOLECULAR MODELING'''
* ''Classical Force Fields''
: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.mov mov] [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]
|-
| <center>2023.09.25 Mon</center>
|
* ''Classical Force Fields''
:1. OPLS
:2. AMBER
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.mp4 Pina, Liliana mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk01.pdf  pdf]
<br>
2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.25.AMS535.talk02.mp4 Bickel, John 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]

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]

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>
|
*''Explicit Solvent Models''
:1. Water models (TIP3P, TIP4P, SPC)
:2. Condensed-phase calculations (DGhydration)
| 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.09.27.AMS535.talk01.mp4  Boysan, Brock 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 Dwulit, Catherine 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]

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]

|-
| <center>2023.10.02 Mon</center>
|
*''Continuum Solvent Models''
:1. Generalized Born Surface Area (GBSA)
: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  Bushati, Aldo 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  Dreher, Kathleen 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]

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>
|-

|- style="background:lightgreen"
| <center>-</center>
||<center>-</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> 
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'''
*''Molecular Conformations''
:1. Small molecules, peptides, relative energy, minimization methods
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.mp4  Kim, Joseph mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.04.AMS535.talk01.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/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]
|- style="background:peachpuff"
  | <center>2023.10.09 Mon</center>
  | 
*''No Class: Fall Break''
  | <center>-</center>
  | <center>-</center>
  | <center>-</center>
|-
  | <center>2023.10.11 Wed </center>
  | 
*''Sampling Methods for Large Simulations''
:1. Molecular dynamics (MD)
:2. Monte Carlo (MC)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.mp4 Zhu, Zeru mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.11.AMS535.talk02.mp4 Wodzenski, Nicholas mp4] [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/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/Luke001.pdf Metropolis Monte Carlo Simulation Tutorial, LearningFromTheWeb.net, Accessed Oct 2008, Luke, B.]

2. [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/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'' 
:1. Ab initio structure prediction (protein-folding)
*''Predicting Protein Structure''
:2. Example Trp-cage
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.mp4  Corbo, Chris mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk01.pdf   pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.16.AMS535.talk02.mp4  Dharan, Aishwarya mp4] [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/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/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/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. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.18.AMS535.talk01.mp4 Kang, Sung Jin mp4][https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.18.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.18.AMS535.talk02.mp4 Glukhov, Ernest mp4] [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/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]
2. [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]
  | 
|-
  | <center>2023.10.23 Mon</center>
  | 
*''Predicting Protein Structure''
:1. Accelerated MD for Blind Protein Prediction
:2. 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 Aywa, Khalayi mp4 ] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk01.pdf  pdf]


2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.23.AMS535.talk02.mp4 Bickel, John mp4 ] [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]
|-

|- style="background:lightgreen"
| <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'''
*''Docking''
:1. Introduction to DOCK
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.mp4 Corbo, Chris mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.25.AMS535.talk01.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/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''
:1. Test Sets (database enrichment) 
:2. Test Sets (virtual screening)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.mp4 Dreher, Kathleen mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk01.pdf   pdf] 

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.10.30.AMS535.talk02.mp4 Bushati, Aldo mp4] [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/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/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://zinc.docking.org ZINC Website at UCSF, Shoichet group]
|-
  | <center>2023.11.01 Wed</center>
  | 
*''Docking'' 
:1. Footprint-based scoring

*''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 Nguyen, An Phuc mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk01.pdf   pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk02.mp4 Boysan, Brock mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.01.AMS535.talk02.pdf  pdf]
  | 1. [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/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'' 
:1. COMFA
:2 Pharmacophores
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.mp4 Alseika, Zachary mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.06.AMS535.talk02.mp4 Dwulit, Catherine mp4] [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''']

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]
|-
  | <center>2023.11.08 Wed</center>
  | 
*''Discovery Methods.'' 
:1. Pharmacophores
:2. De novo design
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.mp4 Zhu, Zeru mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.08.AMS535.talk02.mp4 Corbo, Chris mp4]
[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 ]

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>2023.11.13 Mon</center>
  | 
*''Discovery Methods'' 
:1. De novo design
:2. Genetic Algorithm
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.mp4 Pak, Steven mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.13.AMS535.talk02.mp4 Bickel, John mp4]
[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/PrentisSingleton001.pdf Prentis, L and Singleton, C et al.; A molecular evolution algorithm for ligand design in DOCK ''J Comp Chem'' '''2022''', ''43 (29)'', 1942-1963]

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>
|-

|- style="background:lightgreen"
| <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
*''Free Energy Methods''
:1. Thermolysin with two ligands (FEP)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.mp4  Kang, Sung Jin mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.15.AMS535.talk01.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/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/Jorgensen006.pdf Jorgensen, W. L., Free Energy Calculations:  A Breakthrough for Modeling Organic Chemistry in Solution. ''Accounts Chem. Res.'' '''1989''', ''22'', 184-189]

1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kollman007.pdf Kollman, P., Free Energy Calculations:  Applications to Chemical and Biochemical Phenomena. ''Chem. Rev.'' '''1993''', ''93'', 2395-2417]
|-
  | <center>2023.11.20 Mon</center>
  | 
*''Free Energy Methods''
:1. Fatty acid synthase I ligands (TI)

*'' MM-PB/GBSA''
:2. Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.mp4  Dharan, Aishwarya mp4] [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk01.pdf   pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.20.AMS535.talk02.mp4  Pina, Liliana mp4] [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/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/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. See above papers

1. [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/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]
|- style="background:peachpuff"
  | <center>2021.11.22 Wed</center>
  | 
*''No Class: Thanksgiving''
  | <center>-</center>
  | <center>-</center>
  | <center>-</center>
|-
  | <center>2023.11.27 Mon </center>
  | *''MM-GBSA case 
:1. EGFR and mutantsstudies''
:2. ErbB family selectivity
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.mp4 Rizzo, Robert mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.22.AMS535.talk02.mp4 Aywa, Khalayi mp4][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/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/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]
  | <center>-</center>
|-
  | <center>2023.11.29 Wed </center>
  | 
*''Linear Response''
:1. Intro to Linear Response (LR method) 
:2. Inhibition of protein kinases (Extended LR method)
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk01.mp4  Wodzenski, Nicholas mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.mp4  Glukhov, Ernest mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.11.29.AMS535.talk02.pdf  pdf]
  | 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/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]
  | <center>-</center>
|-
  | <center>2023.12.04 Mon </center>
  | 
*''Properties of Known Drugs''
:1. Molecular Scaffolds (frameworks) and functionality (side-chains)
:2. Lipinski Rule of Five
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.mp4 Kim, Joseph mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.04.AMS535.talk02.mp4  Boysan, Brock mp4]
[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/Murcko001.pdf Bemis, G. W.; Murcko, M. A., The properties of known drugs. 1. Molecular frameworks. ''J. Med. Chem.'' '''1996''', ''39'', 2887-93]

1. [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/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/Lipinski001.pdf Lipinski, C. A., Chris Lipinski discusses life and chemistry after the Rule of Five. ''Drug. Discov. Today'' '''2003''', ''8'', 12-6]
|-
  | <center>2023.12.06 Wed </center>
  | 
*''Properties of Known Drugs''

:1 ADME Prediction
:2. QED
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.mp4  Nguyen, An Phuc mp4]
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk01.pdf  pdf]

2. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.06.AMS535.talk02.mp4  Pak, Steven mp4]
[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/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/matos_pak_2023.pdf Matos, DRG; Pak, S; Rizzo R; Descriptor-Driven de Novo Design Algorithms for DOCK6 Using RDKit. ''J. Chem. Inf. Model.'' '''2023''']
  | 1. [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]
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||<center>'''IN CLASS QUIZ for Section 5 2023.12.11 MON'''</center>
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  | <center>2023.12.11 Mon </center>
  | 
*''From Target to Market''
:1. Drug Discovery Overview
:2. Attrition Rates
  | 1. [https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.mp4  Bickel, John mp4]
<br>
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2023.12.11.AMS535.talk01.pdf  pdf]
  | 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''.]
  | <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''']
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020.11.30.ams535_thermo_cycles_study_guide.pdf Thermodynamic Cycles] 
<br>
[https://ringo.ams.stonybrook.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2020.11.30.ams535.course_topic_wrapup.pdf Course Wrap-Up Topics]
</center>
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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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