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

  1. Introduction, history, irrational vs. rational
  2. Viral Targets (HIV example)

R. Rizzo

Kuntz004.pdf

and presentation

UNAIDS001.pdf

Krug001.pdf

Turnbull001.pdf

Frankel001.pdf

2004/09.08

Chemistry Review

  1. Molecular structure, bonding, graphical representations
  2. Functionality, properties of organic molecules

R. Rizzo

presentation

 
2004.09.13

Biomolecular Structure

  1. Lipids, carbohydrates
  2. Nucleic acids, proteins

R. Rizzo

presentation

 
2004.09.15

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

presentation

 
2004.09.20

Experimental Techniques for Elucidating Structure

  1. Crystallography, NMR
  2. Molecular databases (PDB, Cambridge) PDB in detail
R. Rizzo presentation  
 

MOLECULAR MODELING

(5 meetings)

 

 

 
2004.09.22

All Atom Force Fields (Molecular Mechanics)

  1. Classical models for simulations
  2. 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

  1. Explicit water models (TIP3P, TIP4P, SPC)
  2. 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

  1. Application: Free Energy of Hydration

V. Badal

Jorgensen010.pdf

 
2004.10.04

Intro. to Thermodynamics

  1. Guest Lecture

C. Simmerling

   
2004.10.06

Intro. to Thermodynamics

  1. Guest Lecture

C. Simmerling

(see above)

   
         
 

SAMPLING METHODS

(5 meetings)

 

 

 

2004.10.11

Conformational Space

  1. Energy minimization methods in drug design
  2. Accommodating protein flexibility in drug design

Y. Kang

C. Marai

Holloway002.pdf

Mccammon001.pdf


Holloway001.pdf

2004.10.13

Molecular Dynamics (MD)

  1. MD simulation method introduction
  2. MD project P3ME

A. Okur

B. Fang

Petsko001.pdf

 
2004.10.18

Metropolis Monte Carlo (MC)

  1. Theory, Simulation analysis, thermodynamic properties
  2. MD vs MC study

B. Strockbine

B. Fang

Metropolis001.pdf

Jorgensen007.pdf


2004.10.20

Enhanced Sampling Techniques

  1. Simulated annealing
  2. 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

  1. Comparative (homology) modeling
  2. Free Energy Calculations

D. Papamichail

L. Wickstrom

Sali001.pdf

Kollman007.pdf

Sali002.pdf

Jorgensen006.pdf

 

LEAD DISCOVERY

(5 meetings)

 

 

 
2004.10.27

Docking I.

  1. Introduction to DOCK program
  2. 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.

  1. Consensus scoring
  2. Molecular representation formats (SMILES, mol2)

P. Saumyadipta

G. Han

Charifson002.pdf

smiles.html

Sybylmol2.pdf

 

2004.11.03

Discovery Methods I.

  1. Pharmacaphores in drug design
  2. De nova design using a genetic algorithm

P. Rissland

Y. Kang

Lam001.pdf

Pegg001.pdf

Kubinyi001.pdf

2004.11.08

Discovery Methods II.

  1. Hotspot probes (GRID program)
  2. COMFA

V. Badal

Z. Huang

Goodford001.pdf

Kubinyi002.pdf

Bunce001.pdf

2004.11.10

Discovery Methods Applications

  1. Human Carbonic Anhydrase
  2. 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)

  1. Thermolysin with 2 ligands
  2. 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

  1. Intro to Linear Response (LR) Method
  2. 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

  1. Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface Area methods
  2. 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

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

S. Wang

M. Layten

Murcko001.pdf

Murcko002.pdf

Lipinski002.pdf

Lipinski001.pdf

2004.12.01

Property Prediction

  1. ADME: Aqueous solubility
  2. 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

  1. Development of MM-PBSA and MM-GBSA methods

Catalin

Kollman003.pdf

 
2004.12.08

Enhanced Sampling Revisited

  1. Replica Exchange
A. Okur    
     

 

 
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