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

  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

09/12/2005

Workshop on Multi-Teraflop Computing in
Biology, Materials & Energy Science

  1. Location: Wang Center
  2. Organizers: Brookhaven National Laboratory, IBM, and Stony Brook
Website    
09/16/2005

Chemistry Review

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

R. Rizzo

presentation

 
09/19/2005

Biomolecular Structure

  1. Lipids, carbohydrates
  2. Nucleic acids, proteins

R. Rizzo

presentation

 
09/23/2005

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

rizzo.lect.005.pdf
 

MOLECULAR MODELING

(5 meetings)

 

 

 
09/26/2005

Introduction to Thermodynamics

  1. Guest Lecture
  2. Guest Lecture

C. Simmerling

presentation

 
09/30/2005

Stony Brook Symposium on New Horizons in Organic Chemistry

  1. Location: Wang Center
  2. Organizers: Stony Brook

Website

 

 
10/03/2005

No Class (Rosh Hashanah)

 

 

 

10/07/2005

All Atom Force Fields (Molecular Mechanics)

  1. Classical models for simulations
  2. 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

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

D. Allmer

X. Liu

Jorgensen003.pdf

Jorgensen010.pdf

Jorgensen008.pdf

10/14/2005

Continuum Solvent Models

  1. Poisson-Boltzmann Surface Area (PBSA)
  2. Generalized Born Surface Area (GBSA)

A. Carr

J. Choi

Honig001.pdf

Still001.pdf

 
 

SAMPLING METHODS

(5 meetings)

 

 

 

10/17/2005

Molecular Conformation

  1. Small molecules, peptides, relative energy
  2. 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

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

P. Woo

C. Hili

Petsko001.pdf

Metropolis001.pdf

Jorgensen007.pdf

10/24/2005

Predicting Protein Structure I.

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

Y. Cheng

X. Liu

Dill001.pdf

Simmerling002.pdf

Anfinsen001.pdf
Fersht001.pdf

10/28/2005

Predicting Protein Structure II.

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

D. Allmer

J. Choi

Sali001.pdf

Moult002.pdf

Sali002.pdf
Moult001.pdf

10/31/2005

Enhanced Sampling Techniques

  1. Simulated annealing
  2. 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.

  1. Introduction to DOCK
  2. Validation Test Sets

S. Mukherjee

Y. Chen

 

Kuntz002.pdf

Taylor001.pdf

Kuntz005.pdf

Kuntz006.pdf

Kuntz003.pdf

Kuntz007.pdf

11/07/2005

Docking II.

  1. Molecular representation
  2. ZINC database for virtual screening

N. Carrascal

A. Carr

Sybylmol2.pdf

Shoichet001.pdf

smiles.html

zinc database

11/11/2005

Discovery Methods I.

  1. Pharmacaphores in drug design
  2. De nova design

C. Hili

P. Woo

Lam001.pdf

Pegg001.pdf

Kubinyi001.pdf

11/14/2005

Discovery Methods II.

  1. Hotspot probes (GRID program)
  2. COMFA

N. Carrascal

J. Choi

Goodford001.pdf

Kubinyi002.pdf

Bunce001.pdf

11/18/2005

Discovery Methods Applications

  1. Human Carbonic Anhydrase
  2. Estrogen Receptor
  3. 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)

  1. Thermolysin with 2 ligands
  2. HIV protease with R vs S ligand
  3. 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

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

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

  1. Inhibition of HIVRT using MC with extended linear response (ELR)
  2. Molecular Scaffolds (frameworks) and functionality (side-chains)
  3. 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

  1. ADME: Aqueous solubility
  2. 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

  1. Dr. Elizabeth Buck, OSI Pharmaceuticals

Website

 

 
     

 

 
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