View source for 2010 AMS-535 Fall

[[Past Announcements]]

'''Current Announcements'''

*Posted on 09/07/2010 by Lingling
:#'''The PPT for Wednesday's class is available online now.'''
:#'''The presentation schedule is posted. Further modification is needed.'''
:#'''Everyone in the class should be getting an email from me about the presentation schedule. For those who didn't fill in the contact sheet in the first two classes, please email me and let me know your email address. Do email me as well if you don't get my email.'''


== Example Quiz/Exam Questions from Prior Semesters ==
[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/ams535.example.questions.pdf example.questions.pdf]

== Course Participants, Topics, References, and 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>2010.08.30 Mon</center>
|| 
*''Organizational Meeting
|| <center>-</center>
|| <center>-</center>
|| <center>-</center>
|-

| <center>2010.09.01 Wed</center>
||
'''SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE'''

*''Drug Discovery''
#Introduction, history, irrational vs. rational
#Viral Target Examples
||[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.01.ams535.rizzo.lect.001.pdf Rizzo, R.]
||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.09.06 Mon</center>
|| 
*''No Class: Labor Day''
||<center>-</center>
||<center>-</center>
||<center>-</center>
|-

| <center>2010.09.08 Wed</center>
|| 
*''Chemistry Review''
#Molecular structure, bonding, graphical representations 
#Functionality, properties of organic molecules 
<center>'''Class ends at 5:00PM'''</center>
||[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.08.ams535.rizzo.lect.002.pdf Rizzo, R.]
|| <center>presentation</center>
|| <center>-</center>
|-

| <center>2010.09.13 Mon</center>
|| 
*''Biomolecular Structure''
#Lipids, carbohydrates 
#Nucleic acids, proteins  
||[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.13.ams535.rizzo.lect.003.pdf Rizzo, R.]
|| <center>presentation</center>
|| <center>-</center>
|-

| <center>2010.09.15 Wed</center>
|| 
*''Molecular Interactions and Recognition''
#Electrostastics, VDW interactions, hydrophobic effect, molecular recognition (binding energy) 
#Inhibitors types: allosteric, transition state, covalent vs non-covalent, selective, competitive  
||[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.15.ams535.rizzo.lect.004.pdf Rizzo, R.]
|| <center>presentation</center>
|| <center>-</center>
|-

|- style="background:paleturquoise"
| <center>2010.09.20 Mon
'''Class in diff location and time'''</center>
|| *''CHE-607 Modern Drug Design and Discovery: Computational Biology Lectures'' 
|| 
1. Simmerling, C.

2. Rizzo, R. 
|| <center>'''NOTE:
For today only we will merge with Professor Ojima's "Modern Drug Design and Discovery" class.

CLASS ROOM CHANGE and TIME CHANGE:

Chemistry Department Room 410, 3:20PM - 5:20PM'''</center>
|| <center>-</center>
|-

| <center>2010.09.22 Wed</center>
|| 
*''Intro. to Methods in 3-D Structure Determination''
#Crystallography, NMR 
#Structure Quality, PDB in detail 
||[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.22.ams535.rizzo.lect.005.pdf Rizzo, R.]
|| <center>presentation</center>
|| <center>-</center>
|-

| <center>2010.09.27 Mon</center>
||
<center>'''Quiz Prior Section I'''</center>

'''SECTION II: MOLECULAR MODELING'''
*''Classical Force Fields''
#All-atom Molecular Mechanics 
||

''Guest Lecture''

[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.27.ams535.talk01.pdf Balius, T.]
||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.09.29 Wed</center>
|| 
*''Force Field Development'' 
#OPLS 
#AMBER  
||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.29.ams535.talk01.pdf Akter, R.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.09.29.ams535.talk02.pdf Cao, Y.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.10.04 Mon</center>
|| 
*''Explicit Solvent Models''
#Water models (TIP3P, TIP4P, SPC) 
#Condensed-phase calculations (DGhydration)
||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.04.ams535.talk01.pdf  Chen, J.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.04.ams535.talk02.pdf  Conte, M.]


||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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]

||<center>-</center>
|-

| <center>2010.10.06 Wed</center>
|| 
*''Continuum Solvent Models''
#Generalized Born Surface Area (GBSA)
#Poisson-Boltzmann Surface Area (PBSA)  

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.06.ams535.talk01.pdf  Efaplomatides, C.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.06.ams535.talk02.pdf  Fochtman, B.]

||

1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.10.11 Mon</center>
||
<center>'''Quiz Prior Section II'''</center>

'''SECTION III: SAMPLING METHODS'''
*''Molecular Conformation''
#Small molecules, peptides, relative energy, minimization methods

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.11.ams535.talk01.pdf  Gardin, J.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.10.13 Wed</center>
|| 
*''Primary Sampling Methods for Computer Simulations''
#Molecular dynamics (MD) 
#Monte Carlo (MC)

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.13.ams535.talk01.pdf  Maringano, D.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.13.ams535.talk02.pdf  Hambardzhieva, E.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Luke001.pdf Metropolis Monte Carlo Simulation Tutorial, LearningFromTheWeb.net, Accessed Oct 2008, Luke, B.]

2. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.10.18 Mon</center>
|| 
*''Predicting Protein Structure I.'' 
#Ab initio prediction (protein-folding) 
#Example Trp-cage

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.18.ams535.talk01.pdf  Grinshpun, B.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.18.ams535.talk02.pdf  Hancewicz, J.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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]

||
1-2. [http://rizzo.ams.sunysb.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]
|-

| <center>2010.10.20 Wed</center>
|| 
*''Predicting Protein Structure II.'' 
#Comparative (homology) modeling 
#Case studies (CASP)

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.20.ams535.talk01.pdf  Jee, J.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.20.ams535.talk02.pdf  Jin, X.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Moult002.pdf Moult, J., A decade of CASP: progress, bottlenecks and prognosis in protein structure prediction. ''Curr. Opin. Struct. Biol.'' '''2005''',''15'', 285-9]

||
1. [http://rizzo.ams.sunysb.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]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Moult003.pdf Kryshtafovych, A.; et al., Progress over the first decade of CASP experiments. ''Proteins'' '''2005''', ''61 Suppl 7'', 225-36]
|-

| <center>2010.10.25 Mon</center>
|| 
*''Enhanced Sampling Techniques''
#Simulated annealing 
#Protein Design 

||

''Guest Lecture''

[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.25.ams535.talk01.pdf  Au, L.]

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Brunger001.pdf Brunger, A. T.;Adams, P. D., Molecular dynamics applied to X-ray structure refinement. ''Acc. Chem. Res.'' '''2002''', ''35'', 404-12]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Street001.pdf Street, A. G.; Mayo, S. L., Computational protein design. ''Structure.'' '''1999''', ''7'', 105-9]

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Brunger004.pdf Adams, P. D.; et al., Extending the limits of molecular replacement through combined simulated annealing and maximum-likelihood refinement. ''Acta Crystallogr D Biol Crystallogr'' '''1999''', ''55'', 181-90]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Lippow001.pdf Lippow, S. M.; Tidor, B., Progress in computational protein design. ''Curr. Opin. Biotechnol.'' '''2007''', ''18'', 305-311]
|-

| <center>2010.10.27 Wed</center>
||
<center>'''Quiz Prior Section III'''</center>


'''SECTION IV: LEAD DISCOVERY'''
*''Docking I.''
#Introduction to DOCK
||
''Guest Lecture''

[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.10.27.ams535.talk01.pdf Mukherjee, S.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo014.pdf Moustakas, D. T.; et al., Development and Validation of a Modular, Extensible Docking program: DOCK 5. ''J. Comput. Aided Mol. Des.'' '''2006''', ''20'', 601-619]
|-

| <center>2010.11.01 Mon</center>
|| 
*''Discovery Methods I.'' 
#Hotspot probes (GRID) 
#COMFA 

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.01.ams535.talk01.pdf  Lee, S.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.01.ams535.talk02.pdf  Lei, L.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Kubinyi002.pdf Kubinyi, H., Encyclopedia of Computational Chemistry, ''Databases and Expert Systems Section'', John Wiley & Sons, Ltd. '''1998''']

||
1. [http://rizzo.ams.sunysb.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>2010.11.03 Wed</center>
||
*''Discovery Methods II.'' 
#Pharmacaphores in drug design 
#De nova design 

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.03.ams535.talk01.pdf  Ashiru-Balogun, J.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.03.ams535.talk02.pdf  Li, M.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.11.08 Mon</center>
|| 
*''Docking II.'' 
#Test Sets (binding modes) 
#Test Sets (virtual screening)

||
''Guest Lecture''

[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.08.ams535.talk01.pdf Mukherjee, S.]

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Taylor001.pdf Nissink, J. W. M.; et al., A new test set for validating predictions of protein-ligand interaction. ''Prot. Struct. Funct. Genetics'' '''2002''', ''49'', 457-471]

2. [http://rizzo.ams.sunysb.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. [http://www.ccdc.cam.ac.uk/products/life_sciences/gold/validation/astex/ The CCDC/Astex Test Set]

2. [http://zinc.docking.org ZINC - A free database of commercially-available compounds for virtual screening]
|-

| <center>2010.11.10 Wed</center>
|| 
*''Docking III.''
#''Enrichment and Rescoring''

||
''Guest Lecture''
[http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.10.ams535.talk01.pdf Balius, T.]

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Shoichet002.pdf Huang, N.; et al., Benchmarking Sets for Molecular Docking. ''J. Med. Chem.'' '''2006''', ''49(23)'', 6789-6801]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Deng001.pdf Deng, Z; et al., Knowledge-Based Design of Target-Focused Libraries Using Protein-Ligand Interaction Constraints. ''J. Med. Chem.'' '''2006''', ''49'', 490-500]

||
<center>-</center>
|-

| <center>2010.11.15 Mon</center>
||
<center>'''Quiz Prior Section IV'''</center>


'''SECTION V: LEAD REFINEMENT
*''Free Energy Perturbation (FEP'')
#Thermolysin with two ligands 

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.15.ams535.talk01.pdf  Li, Z.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.11.17 Wed </center>
|| 
*''Thermodynamic Integration''
#Free energy calculation using TI 
#TI case study

||

1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.17.ams535.talk01.pdf  Liao, J.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.17.ams535.talk02.pdf TBA. ]
||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/TBA.pdf TBA; ]

||<center>-</center>
|-

| <center>2010.11.22 Mon </center>
|| 
*''MM-PBSA, MM-GBSA, TI''
#Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods 
#TI and MM-GBSA 

||

1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.22.ams535.talk01.pdf  Liu, J.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.22.ams535.talk02.pdf  Liu, Y.]

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1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/Cai001.pdf Cai, Y.; Schiffer, C. A.; Decomposing the Energetic Impact of Drug Resistant Mutations in HIV-1 Protease on Binding DRV. ''J. Chem. Theory Comput.'' '''2010''', ''6'', 1358-1368]

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|- style="background:peachpuff"
| <center>2010.11.24 Wed</center>
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*''No Class: Following a Friday schedule''

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| <center>2010.11.29 Mon</center>
|| 
*''MM-GBSA case studies''
#EGFR
#HIVgp41 


||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.29.ams535.talk01.pdf  Messina, D.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.11.29.ams535.talk02.pdf  Spaqnuolo, L.]

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo019.pdf Balius, T.; Rizzo, R. C.; Quantitative Prediction of Fold Resistance for Inhibitors of EGFR. ''Biochemistry'' '''2009''', ''48'', 8435-8448]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/References/rizzo015.pdf Strockbine, B.; Rizzo, R. C., Binding of Anti-fusion Peptides with HIVgp41 from Molecular Dynamics Simulations: Quantitative Correlation with Experiment. ''Prot. Struct. Funct. Bioinformatics'' '''2007''', ''63'', 630-642]

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| <center>2010.12.01 Wed </center>
|| 
*''Linear Response'' 
#Intro to Linear Response (LR method) 
#Inhibition of protein kinases (Extended LR method) 

||
1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.01.ams535.talk01.pdf  Van Wart, T.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.01.ams535.talk02.pdf  Yang, R.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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]

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|-



| <center>2010.12.06 Mon </center>
|| 

*''Properties of Known Drugs''
#Lipinski Rule of Five
#ADME prediction

||

1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.06.ams535.talk01.pdf  Yao, Y.]

2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.06.ams535.talk02.pdf  Yerramilli, V.]


|| 

1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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>2010.12.08 Wed </center>
||
*''Properties of Known Drugs and Protein Structure Prediction III.''
#Molecular Scaffolds (frameworks) and functionality (side-chains)
#TBA

||

1. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.06.ams535.talk01.pdf  Yu, W.]


2. [http://rizzo.ams.sunysb.edu/~rizzo/StonyBrook/teaching/AMS532_AMS535_AMS536/Presentations/2010.12.06.ams535.talk02.pdf  TBA.]

||
1. [http://rizzo.ams.sunysb.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. [http://rizzo.ams.sunysb.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. TBA

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2. TBA
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|- style="background:gold"
| <center>2010.12.13 Mon</center>
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<center>'''FINAL EXAM'''</center>
<center>'''MON'''</center>
<center>'''TIME TBA</center>

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||<center>'''NOTE:

Unless otherwise noted the Final will be given in our regular class room.''' 

FINAL EXAM IS CUMULATIVE
</center>

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