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

  1. Introduction, history, irrational vs. rational
  2. 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

  1. Molecular structure, bonding, graphical representations
  2. 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

  1. Lipids, carbohydrates
  2. 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 **

  1. 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

  1. Electrostastics, VDW interactions, hydrophobic effect, molecular recognition (binding energy)
  2. 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

  1. Crystallography, NMR
  2. 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

  1. All-atom Molecular Mechanics

W. Berger

Mackerell001.pdf

vangunsteren003.pdf

2007.10.03

Wed

Force Field Development

  1. OPLS
  2. AMBER

G. Barsegian

M. Bourassa

 

Jorgensen002.pdf

Kollman004.pdf

 

 

Jorgensen004.pdf

Jorgensen005.pdf

Kollman005.pdf

Kollman006.pdf

 

2007.10.08

Mon

Explicit Solvent Models

  1. Water models (TIP3P, TIP4P, SPC)
  2. Condensed-phase calculations (DGhydration)

G. Chen

N. Hai

Jorgensen003.pdf

Jorgensen010.pdf

Jorgensen008.pdf

2007.10.10

Wed

Continuum Solvent Models

  1. Poisson-Boltzmann Surface Area (PBSA)
  2. 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

  1. 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

  1. Molecular dynamics (MD)
  2. Monte Carlo (MC)

J. Lee

X. Li

Petsko001.pdf

Metropolis001.pdf

Jorgensen007.pdf

2007.10.22

Mon

Predicting Protein Structure I.

  1. Ab initio prediction (protein-folding)
  2. Example Trp-cage

N. Li

L. Liu

Dill001.pdf

Simmerling002.pdf

Anfinsen001.pdf
Fersht001.pdf

2007.10.24

Wed

Predicting Protein Structure II.

  1. Comparative (homolgy) modeling
  2. Case studies (CASP)

C. Martinez

W. Meng

Sali001.pdf

Moult002.pdf

Sali002.pdf
Moult001.pdf

2007.10.29

Mon

Enhanced Sampling Techniques

  1. Simulated annealing
  2. 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.

  1. Introduction to DOCK

S. Mukherjee

Kuntz002.pdf

Kuntz005.pdf

Kuntz006.pdf

Kuntz003.pdf

Kuntz007.pdf

2007.11.05

Mon

Docking II.

  1. Test Sets (binding modes)
  2. Test Sets (virtual screening)

S. Mukherjee

Taylor001.pdf

Shoichet001.pdf

Sybylmol2.pdf

smiles.html

zinc.html

2007.11.07

Wed

Discovery Methods I.

  1. Pharmacaphores in drug design
  2. De nova design

L. Palmer

P. Pan

Lam001.pdf and Bhattacharjee001.pdf

Pegg001.pdf

Kubinyi001.pdf

2007.11.12

Mon

Discovery Methods II.

  1. Hotspot probes (GRID)
  2. COMFA

S. Peng

A. Rao

Goodford001.pdf

Kubinyi002.pdf

Bunce001.pdf

2007.11.14

Wed

Discovery Methods Applications

  1. Human Carbonic Anhydrase
  2. Estrogen Receptor

R. Wang

S. Xiao

Klebe001.pdf

Waszk001.pdf

Tamoxifen001.pdf

         

2007.11.19

Mon

SECTION V:
LEAD REFINEMENT

Free Energy Perturbation (FEP)

  1. Thermolysin with 2 ligands
  2. 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

  1. Intro to Linear Response (LR method)

Y.Zhang

Aqvist001.pdf

Aqvist002.pdf

2007.11.28

Wed

MM-PBSA, MM-GBSA

  1. Inhibition of protein kinases (Extended LR method)
  2. 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

  1. MM-GBSA case studies

R. Rizzo

rizzo015.pdf

rizzo010.pdf

Chan001.pdf

2007.12.05

Wed

Properties of Known Drugs

  1. Molecular Scaffolds (frameworks) and functionality (side-chains)
  2. Lipinski "rule of 5"

B. McGillick

Murcko001.pdf

Murcko002.pdf

Lipinski002.pdf

Lipinski001.pdf

2007.12.10

Mon

Guest Lecture

  1. 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