AMS 535 Syllabus

2007 Fall Course Syllabus: AMS-535

Introduction to Computational Structural Biology and Drug Design

Fall 2007

Instructor:	Dr. Robert C. Rizzo [631-632-8519, rizzorc@gmail.com]
Course:	AMS-535 (3 Credits / 0 Audit) http://www.ams.sunysb.edu/~rizzo (go to Teaching)
When:	Monday/Wednesday, 3:50-5:10 PM, Stony Brook Union, Room 237
Office Hours:	Anytime (call first) or by appointment, Room 3-129, Dept. of Applied Math & Statistics

COMPANION COURSE: A companion course taught in the Spring (AMS-536, "Molecular Modeling of Biological Molecules") gives hands-on experience in using computational methods discussed in the introductory Fall course. Students interested in taking the two-semester sequence should plan accordingly since AMS-535 (Fall) is a prerequisite for AMS-536 (Spring).

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 myself, 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. Grades will be based on the quality of the talks, participation in class discussion, attendance, quizzes, and a final.

DISABILITY SUPPORT SERVICES (DSS) STATEMENT: If you have a physical, psychological, medical, or learning disability that may impact your course work, please contact Disability Support Services (631) 632-6748 or http://studentaffairs.stonybrook.edu/dss/ They will determine with you what accommodations are necessary and appropriate. All information and documentation is confidential.

Students who require assistance during emergency evacuation are encouraged to discuss their needs with their professors and Disability Support Services. For procedures and information go to the following website: http://www.stonybrook.edu/ehs/fire/disabilities

ACADEMIC INTEGRITY STATEMENT: Each student must pursue his or her academic goals honestly and be personally accountable for all submitted work. Representing another person's work as your own is always wrong. Faculty are required to report any suspected instance of academic dishonesty to the Academic Judiciary. For more comprehensive information on academic integrity, including categories of academic dishonesty, please refer to the academic judiciary website at http://www.stonybrook.edu/uaa/academicjudiciary

CRITICAL INCIDENT MANAGEMENT: Stony Brook University expects students to respect the rights, privileges, and property of other people. Faculty are required to report to the Office of Judicial Affairs any disruptive behavior that interrupts their ability to teach, compromises the safety of the learning environment, and/or inhibits students' ability to learn.

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

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.

EXAMPLE QUESTIONS FROM PREVIOUS EXAMS: 2007.ams535.example.questions.pdf

Date	Topics	Speaker and Presentation	Primary Reference	Secondary References
2007.09.05 Wed	Organizational Meeting

2007.09.10 Mon	SECTION I: DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE Drug Discovery Introduction, history, irrational vs. rational Viral Target Examples	R. Rizzo	Note: This presentation contain slides from a variety of online sources for educational and illustrative purposes only. Kuntz004.pdf Jorgensen009.pdf
2007.09.12 Wed	Chemistry Review Molecular structure, bonding, graphical representations Functionality, properties of organic molecules	R. Rizzo	Note: This presentation contain slides from a variety of online sources for educational and illustrative purposes only.
2007.09.17 Mon	Biomolecular Structure Lipids, carbohydrates Nucleic acids, proteins	R. Rizzo	Note: This presentation contain slides from a variety of online sources for educational and illustrative purposes only.
2007.09.19 Wed	Special Lecture NOTE ROOM CHANGE Chemistry Room 412 A Replica-exchange Molecular Dynamics Study"	Dr. Yuji Sugita	Sugita002.pdf	Mark001.pdf Shea001.pdf Sugita001.pdf
2007.09.24 Mon	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	Note: This presentation contain slides from a variety of online sources for educational and illustrative purposes only.
2007.09.26 Wed	Intro. to Methods in 3-D Structure Determination Crystallography, NMR Structure Quality, PDB in detail	R. Rizzo	Note: This presentation contain slides from a variety of online sources for educational and illustrative purposes only.

2007.10.01 Mon	Quiz Prior Section I SECTION II: MOLECULAR MODELING Classical Force Fields All-atom Molecular Mechanics	W. Berger	Mackerell001.pdf	vangunsteren003.pdf
2007.10.03 Wed	Force Field Development OPLS AMBER	G. Barsegian M. Bourassa	Jorgensen002.pdf Kollman004.pdf	Jorgensen004.pdf Jorgensen005.pdf Kollman005.pdf Kollman006.pdf
2007.10.08 Mon	Explicit Solvent Models Water models (TIP3P, TIP4P, SPC) Condensed-phase calculations (DGhydration)	G. Chen N. Hai	Jorgensen003.pdf Jorgensen010.pdf	Jorgensen008.pdf
2007.10.10 Wed	Continuum Solvent Models Poisson-Boltzmann Surface Area (PBSA) Generalized Born Surface Area (GBSA)	B. Henares Y. Huang	Honig001.pdf Still001.pdf

2007.10.15 Mon	Quiz Prior Section II SECTION III: SAMPLING METHODS Molecular Conformation Small molecules, peptides, relative energy, minimization methods	T. Jiang	Kollman011.pdf and NIH001.pdf	MMtutor.pdf Holloway001.pdf
2007.10.17 Wed	Primary Sampling Methods for Computer Simulations Molecular dynamics (MD) Monte Carlo (MC)	J. Lee X. Li	Petsko001.pdf Metropolis001.pdf	Jorgensen007.pdf
2007.10.22 Mon	Predicting Protein Structure I. Ab initio prediction (protein-folding) Example Trp-cage	N. Li L. Liu	Dill001.pdf Simmerling002.pdf	Anfinsen001.pdf Fersht001.pdf
2007.10.24 Wed	Predicting Protein Structure II. Comparative (homolgy) modeling Case studies (CASP)	C. Martinez W. Meng	Sali001.pdf Moult002.pdf	Sali002.pdf Moult001.pdf
2007.10.29 Mon	Enhanced Sampling Techniques Simulated annealing Replica Exchange	P. Mulundi Y. Oum	Brunger001.pdf Sugita001.pdf	Brunger004.pdf Sugita002.pdf

2007.10.31 Wed	Quiz Prior Section III SECTION IV: LEAD DISCOVERY Docking I. Introduction to DOCK	S. Mukherjee	Kuntz002.pdf	Kuntz005.pdf Kuntz006.pdf Kuntz003.pdf Kuntz007.pdf
2007.11.05 Mon	Docking II. Test Sets (binding modes) Test Sets (virtual screening)	S. Mukherjee	Taylor001.pdf Shoichet001.pdf	Sybylmol2.pdf smiles.html zinc.html
2007.11.07 Wed	Discovery Methods I. Pharmacaphores in drug design De nova design	L. Palmer P. Pan	Lam001.pdf and Bhattacharjee001.pdf Pegg001.pdf	Kubinyi001.pdf
2007.11.12 Mon	Discovery Methods II. Hotspot probes (GRID) COMFA	S. Peng A. Rao	Goodford001.pdf Kubinyi002.pdf	Bunce001.pdf
2007.11.14 Wed	Discovery Methods Applications Human Carbonic Anhydrase Estrogen Receptor	R. Wang S. Xiao	Klebe001.pdf Waszk001.pdf	Tamoxifen001.pdf

2007.11.19 Mon	SECTION V: LEAD REFINEMENT Free Energy Perturbation (FEP) Thermolysin with 2 ligands Review for QUIZ IV	L. Xie S. Mukherjee	Kollman009.pdf	Jorgensen006.pdf Kollman007.pdf
2007.11.21 Wed	No Class: University Correction Day
2007.11.26 Mon	Quiz Prior Section IV SECTION V cont: LEAD REFINEMENT Linear Response Intro to Linear Response (LR method)	Y.Zhang	Aqvist001.pdf	Aqvist002.pdf
2007.11.28 Wed	MM-PBSA, MM-GBSA Inhibition of protein kinases (Extended LR method) Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods	R. Goyal T. Balius	Jorgensen001.pdf Kollman012.pdf	rizzo008.pdf
2007.12.03 Mon	MM-GBSA MM-GBSA case studies	R. Rizzo	rizzo015.pdf rizzo010.pdf	Chan001.pdf
2007.12.05 Wed	Properties of Known Drugs Molecular Scaffolds (frameworks) and functionality (side-chains) Lipinski "rule of 5"	B. McGillick	Murcko001.pdf Murcko002.pdf Lipinski002.pdf	Lipinski001.pdf
2007.12.10 Mon	Guest Lecture Working in the Pharmaceutical Industry	Dr. Elizabeth Buck	OSI Pharmaceuticals
2007.12.12 Wed	Review for Final Exam	S. Mukherjee	Note:Final exam is Cumulative
2007.12.19 Wed	FINAL EXAM 5:00 - 7:30 PM		Unless otherwise noted the Final Exam will be given in our regular class room