AMS 535 Syllabus

2004 Fall Course Syllabus: AMS-535

Introduction to Computational Structural Biology and Drug Design

Fall 2004

Instructor:	Dr. Robert C. Rizzo [631-632-9340, rizzo@ams.sunysb.edu]
Course:	AMS-535 (3 Credits / 0 Audit) http://www.ams.sunysb.edu/~rizzo (go to Teaching)
When:	Monday/Wednesday, 2:20-3:40 PM, Room N3063, Library 3rd Floor
Office Hours:	Tues/Fri, 2:00-4:00 PM or by appointment, Room 1-101, Dept. of Applied Math & Statistics
Note:	The original course number was AMS 691 section 2

Hyperlinks accessed through Stony Brook University's electronic journal subscriptions are provided below for educational purposes only.

	DRUG DISCOVERY / BIOMOLECULAR STRUCTURE (6 meetings)
Date	Topics	Speaker and Presentation	Primary Reference	Additional References
2004.08.30	Organizational Meeting
2004.09.01	Drug Discovery Introduction, history, irrational vs. rational Viral Targets (HIV example)	R. Rizzo	Kuntz004.pdf and presentation	UNAIDS001.pdf Krug001.pdf Turnbull001.pdf Frankel001.pdf
2004/09.08	Chemistry Review Molecular structure, bonding, graphical representations Functionality, properties of organic molecules	R. Rizzo	presentation
2004.09.13	Biomolecular Structure Lipids, carbohydrates Nucleic acids, proteins	R. Rizzo	presentation
2004.09.15	Molecular Interactions and Recognition Electrostastics, VDW interactions, hydrophobic effect, molecular recognition (binding energy) Inhibitors types: allosteric, transition state, covalent vs non-covalent, selective, competitive	R. Rizzo	presentation
2004.09.20	Experimental Techniques for Elucidating Structure Crystallography, NMR Molecular databases (PDB, Cambridge) PDB in detail	R. Rizzo	presentation
	MOLECULAR MODELING (5 meetings)
2004.09.22	All Atom Force Fields (Molecular Mechanics) Classical models for simulations Parameter development (OPLS)	S. Rafi A. Ramanathan	Mackerell001.pdf Jorgensen002.pdf	Kollman004.pdf Kollman005.pdf Kollman006.pdf Jorgensen004.pdf Jorgensen005.pdf
2004.09.27	Explicit Solvent Models Explicit water models (TIP3P, TIP4P, SPC) Continuum water models: Poisson-Boltzmann Surface Area, PARSE	S. Wang M. Sharma	Jorgensen003.pdf Honig001.pdf	Honig001.pdf Still001.pdf
2004.09.29	Condensed Phase Calculations Application: Free Energy of Hydration	V. Badal	Jorgensen010.pdf
2004.10.04	Intro. to Thermodynamics Guest Lecture	C. Simmerling
2004.10.06	Intro. to Thermodynamics Guest Lecture	C. Simmerling (see above)

	SAMPLING METHODS (5 meetings)
2004.10.11	Conformational Space Energy minimization methods in drug design Accommodating protein flexibility in drug design	Y. Kang C. Marai	Holloway002.pdf Mccammon001.pdf	Holloway001.pdf
2004.10.13	Molecular Dynamics (MD) MD simulation method introduction MD project P3ME	A. Okur B. Fang	Petsko001.pdf
2004.10.18	Metropolis Monte Carlo (MC) Theory, Simulation analysis, thermodynamic properties MD vs MC study	B. Strockbine B. Fang	Metropolis001.pdf Jorgensen007.pdf
2004.10.20	Enhanced Sampling Techniques Simulated annealing Locally Enhanced Sampling (LES)	A. Ramanathan D. Papamichail	Brunger001.pdf Simmerling001.pdf	Brunger002.pdf Brunger003.pdf Brunger004.pdf Vecchi001.pdf
2004.10.25	Predicting Protein Structure Comparative (homology) modeling Free Energy Calculations	D. Papamichail L. Wickstrom	Sali001.pdf Kollman007.pdf	Sali002.pdf Jorgensen006.pdf
	LEAD DISCOVERY (5 meetings)
2004.10.27	Docking I. Introduction to DOCK program Comparison of docking and scoring methods	X. Chen P. Saumyadipta	Kuntz004.pdf Kuntz002.pdf Charifson001.pdf	Kuntz005.pdf Kuntz006.pdf Kuntz003.pdf Kuntz007.pdf
2004.11.01	Docking II. Consensus scoring Molecular representation formats (SMILES, mol2)	P. Saumyadipta G. Han	Charifson002.pdf smiles.html Sybylmol2.pdf
2004.11.03	Discovery Methods I. Pharmacaphores in drug design De nova design using a genetic algorithm	P. Rissland Y. Kang	Lam001.pdf Pegg001.pdf	Kubinyi001.pdf
2004.11.08	Discovery Methods II. Hotspot probes (GRID program) COMFA	V. Badal Z. Huang	Goodford001.pdf Kubinyi002.pdf	Bunce001.pdf
2004.11.10	Discovery Methods Applications Human Carbonic Anhydrase Estrogen Receptor (breast cancer, osteoporosis)	A. Tovkach C. Marai	Klebe001.pdf Waszk001.pdf	Tamoxifen001.pdf
	LEAD REFINEMENT (5 meetings)
2004.11.15	Binding Energy I. Free Energy Perturbation (FEP) Thermolysin with 2 ligands HIV protease with R vs S ligands	Y. Chen M. Sharma	Kollman009.pdf Kollman002.pdf	Kollman007.pdf
2004.11.17	Binding Energy II. Linear Response Intro to Linear Response (LR) Method Inhibition of protein kinases via MC/ELR	R. Rizzo (chalk) Y. Chen	Aqvist001.pdf Jorgensen001.pdf	Aqvist002.pdf rizzo004.pdf rizzo008.pdf
11.22.2004	Binding Energy III. MM-PBSA, MM-GBSA Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methods Molecular basis of HIV protease drug resistance (MM-PBSA study)	R. Rizzo (chalk) G. Han	Kollman003.pdf Kollman001.pdf
2004.11.29	Properties of Known Drugs Molecular Scaffolds (frameworks) and functionality (side-chains) Lipinski "rule of 5"	S. Wang M. Layten	Murcko001.pdf Murcko002.pdf Lipinski002.pdf	Lipinski001.pdf
2004.12.01	Property Prediction ADME: Aqueous solubility ADME: Blood-Brain-Barrier (BBB)	S. Rafi M. Zhao	Jorgensen011.pdf Xu001.pdf	Guttendorf001.pdf Young001.pdf Xu004.pdf Xu003.pdf
	MISCELLANEOUS (2 meetings)
2004.12.06	Nucleic Acid Stability Development of MM-PBSA and MM-GBSA methods	Catalin	Kollman003.pdf
2004.12.08	Enhanced Sampling Revisited Replica Exchange	A. Okur

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