AMS 535 Syllabus

2005 Fall Course Syllabus: AMS-535

Introduction to Computational Structural Biology and Drug Design

Fall 2005

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/Friday, 12:50-2:10 PM, Room N101, SOCBEHAV SCI
Office Hours:	Anytime or by appointment, Room 1-101, Dept. of Applied Math & Statistics

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
08/29/2005	First class will meet on Friday
09/02/2005	Organizational Meeting
09/05/2005	No class (labor day)
09/09/2005	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
09/12/2005	Workshop on Multi-Teraflop Computing in Biology, Materials & Energy Science Location: Wang Center Organizers: Brookhaven National Laboratory, IBM, and Stony Brook	Website
09/16/2005	Chemistry Review Molecular structure, bonding, graphical representations Functionality, properties of organic molecules	R. Rizzo	presentation
09/19/2005	Biomolecular Structure Lipids, carbohydrates Nucleic acids, proteins	R. Rizzo	presentation
09/23/2005	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	rizzo.lect.005.pdf
	MOLECULAR MODELING (5 meetings)
09/26/2005	Introduction to Thermodynamics Guest Lecture Guest Lecture	C. Simmerling	presentation
09/30/2005	Stony Brook Symposium on New Horizons in Organic Chemistry Location: Wang Center Organizers: Stony Brook	Website
10/03/2005	No Class (Rosh Hashanah)
10/07/2005	All Atom Force Fields (Molecular Mechanics) Classical models for simulations Parameter development	T. Focella Y. Chen	Mackerell001.pdf Jorgensen002.pdf	Kollman004.pdf Kollman005.pdf Kollman006.pdf Jorgensen004.pdf Jorgensen005.pdf
10/10/2005	Explicit Solvent Models Water models (TIP3P, TIP4P, SPC) Condensed-phase calculations (DGhydration)	D. Allmer X. Liu	Jorgensen003.pdf Jorgensen010.pdf	Jorgensen008.pdf
10/14/2005	Continuum Solvent Models Poisson-Boltzmann Surface Area (PBSA) Generalized Born Surface Area (GBSA)	A. Carr J. Choi	Honig001.pdf Still001.pdf
	SAMPLING METHODS (5 meetings)
10/17/2005	Molecular Conformation Small molecules, peptides, relative energy Energy minimization methods	I. Pflaum N. Carrascal	Kollman011.pdf Holloway002.pdf	NIH001.pdf Colby_College_MMtutor.pdf Holloway001.pdf
10/21/2005	Primary Sampling Methods for Computer Simultations Molecular dynamics (MD) Monte Carlo (MC)	P. Woo C. Hili	Petsko001.pdf Metropolis001.pdf	Jorgensen007.pdf
10/24/2005	Predicting Protein Structure I. Ab initio prediction (protein-folding) Example Trp-cage	Y. Cheng X. Liu	Dill001.pdf Simmerling002.pdf	Anfinsen001.pdf Fersht001.pdf
10/28/2005	Predicting Protein Structure II. Comparative (homolgy) modeling Case studies (CASP)	D. Allmer J. Choi	Sali001.pdf Moult002.pdf	Sali002.pdf Moult001.pdf
10/31/2005	Enhanced Sampling Techniques Simulated annealing Locally Enhanced Sampling (LES)	R. Colson I. Pflaum	Brunger001.pdf Roitberg001.pdf	Brunger002.pdf Brunger003.pdf Brunger004.pdf Vecchi001.pdf Simmerling004.pdf
	LEAD DISCOVERY (5 meetings)
11/04/2005	Docking I. Introduction to DOCK Validation Test Sets	S. Mukherjee Y. Chen	Kuntz002.pdf Taylor001.pdf	Kuntz005.pdf Kuntz006.pdf Kuntz003.pdf Kuntz007.pdf
11/07/2005	Docking II. Molecular representation ZINC database for virtual screening	N. Carrascal A. Carr	Sybylmol2.pdf Shoichet001.pdf	smiles.html zinc database
11/11/2005	Discovery Methods I. Pharmacaphores in drug design De nova design	C. Hili P. Woo	Lam001.pdf Pegg001.pdf	Kubinyi001.pdf
11/14/2005	Discovery Methods II. Hotspot probes (GRID program) COMFA	N. Carrascal J. Choi	Goodford001.pdf Kubinyi002.pdf	Bunce001.pdf
11/18/2005	Discovery Methods Applications Human Carbonic Anhydrase Estrogen Receptor GPCRs	Y. Chen T. Focella L. Cui	Klebe001.pdf Waszk001.pdf Becker001.pdf	Tamoxifen001.pdf
	LEAD REFINEMENT (5 meetings)
11/21/2005	Binding Energy I. Free Energy Perturbation (FEP) Thermolysin with 2 ligands HIV protease with R vs S ligand Celebrex binding with COX enzymes	S. Mukherjee C. Hili Y.Cheng	Kollman009.pdf Kollman002.pdf Jorgensen013.pdf	Kollman007.pdf Jorgensen012.pdf
11/25/2005	No class (Thanksgiving)
11/28/2005	Binding Energy II. Linear Response Intro to Linear Response (LR) Method Inhibition of protein kinases via MC/ELR	R. Colson A. Carr	Aqvist001.pdf Jorgensen001.pdf	Aqvist002.pdf rizzo008.pdf
12/02/2005	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)	S. Mukherjee D. Allmer	Kollman003.pdf Kollman001.pdf
12/05/2005	Properties of Known Drugs Inhibition of HIVRT using MC with extended linear response (ELR) Molecular Scaffolds (frameworks) and functionality (side-chains) Lipinski "rule of 5"	X. Liu R. Colson T. Focella	rizzo004.pdf Murcko001.pdf Murcko002.pdf Lipinski002.pdf	Lipinski001.pdf
12/09/2005	Property Prediction ADME: Aqueous solubility ADME: Blood-Brain-Barrier (BBB)	P. Woo Y. Cheng	Jorgensen011.pdf Xu001.pdf	Guttendorf001.pdf Young001.pdf Xu004.pdf Xu003.pdf
12/12/2005	Guest Lecture Dr. Elizabeth Buck, OSI Pharmaceuticals	Website

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