2006 Fall Course Syllabus: AMS-535

Introduction to Computational Structural Biology and Drug Design

 
Fall 2006
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, 12:50-2:10 PM, ESS (Earth and Space Sciences) Room 079
Office Hours:   Anytime (call first) or by appointment, Room 1-101, Dept. of Applied Math & Statistics
 

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, and five quizzes.

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).

 
If you have a physical, psychological, medical, or learning disability that may impact your course work, please contact Disability Support Services (631) 632-6748.  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.ehs.sunysb.edu and search Fire Safety and Evacuation and Disabilities.
 
Hyperlinks accessed through Stony Brook University's electronic journal subscriptions are provided below for educational purposes only.
 
Date
Topics

Speaker and Presentation

Primary Reference

Secondary
References

2006.09.06

Wed

Organizational Meeting
 

 

 
 

 

     

2006.09.11

Mon

 

SECTION I:
DRUG DISCOVERY AND BIOMOLECULAR STRUCTURE

Drug Discovery

  1. Introduction, history, irrational vs. rational
  2. Viral Target Examples

R. Rizzo

presentation

 

and

 

Kuntz004.pdf

Jorgensen009.pdf

 

2006.09.13

Wed

Chemistry Review

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

R. Rizzo

presentation

 

2006.09.18

Mon

Biomolecular Structure

  1. Lipids, carbohydrates
  2. Nucleic acids, proteins

R. Rizzo

presentation

 

2006.09.20

Wed

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

 

2006.09.25

Mon

Intro. to Methods in 3-D Structure Determination

  1. Crystallography, NMR
  2. Structure Quality, PDB in detail

R. Rizzo

presentation

 
 

 

 

 

 

2006.09.27

Wed

 

** Quiz Prior Section I **

SECTION II:
MOLECULAR MODELING

Classical Force Fields

  1. All-atom Molecular Mechanics

Eric

Mackerell001.pdf

vangunsteren003.pdf

2006.10.02

Mon

No Class (Yom Kippur)

 

 

 

2006.10.04

Wed

Force Field Development

  1. OPLS
  2. AMBER

Alvin

Omoz

 

Jorgensen002.pdf

Kollman004.pdf

 

 

Jorgensen004.pdf

Jorgensen005.pdf

Kollman005.pdf

Kollman006.pdf

 

2006.10.09

Mon

Explicit Solvent Models

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

Trent

Christina

Jorgensen003.pdf

Jorgensen010.pdf

Jorgensen008.pdf

2006.10.11

Wed

Continuum Solvent Models

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

Paul

Matthew C.

Honig001.pdf

Still001.pdf

 

2006.10.16

Mon

Guest Lecture: Sequence Alignment and Genomics

  1. Topics TBA

Prof. Steve Skiena

(guest lecture)

presentation

 
 

 

 

 

 

2006.10.18

Wed

 

** Quiz Prior Section II **

SECTION III:
SAMPLING METHODS

Molecular Conformation

  1. Small molecules, peptides, relative energy, minimization methods

Arthur

Kollman011.pdf and NIH001.pdf

MMtutor.pdf
Holloway001.pdf

2006.10.23

Mon

Primary Sampling Methods for Computer Simultations

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

Ricky

Jonathan

Petsko001.pdf

Metropolis001.pdf

Jorgensen007.pdf

2006.10.25

Wed

Predicting Protein Structure I.

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

Ronald

David

Dill001.pdf

Simmerling002.pdf

Anfinsen001.pdf
Fersht001.pdf

2006.10.30

Mon

Predicting Protein Structure II.

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

Diana

Zhou

Sali001.pdf

Moult002.pdf

Sali002.pdf
Moult001.pdf

2006.11.01

Wed

Enhanced Sampling Techniques

  1. Simulated annealing
  2. Locally Enhanced Sampling (LES)

Matt E.

Fangyu

Brunger001.pdf

Roitberg001.pdf

Brunger002.pdf

Brunger003.pdf

Brunger004.pdf

Vecchi001.pdf

Simmerling004.pdf

 

 

 

 

 

2006.11.06

Mon

 

** Quiz Prior Section III **

SECTION IV:
LEAD DISCOVERY

Docking I.

  1. Introduction to DOCK

Yukiji

Kuntz002.pdf

Kuntz005.pdf

Kuntz006.pdf

Kuntz003.pdf

Kuntz007.pdf

2006.11.08

Wed

Docking II.

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

Sudipto Mukherjee

(guest lecture)

Taylor001.pdf

Shoichet001.pdf

Sybylmol2.pdf

smiles.html

zinc.html

2006.11.13

Mon

Discovery Methods I.

  1. Pharmacaphores in drug design
  2. De nova design

Ji

Chen

Lam001.pdf

Pegg001.pdf

Kubinyi001.pdf

2006.11.15

Wed

Discovery Methods II.

  1. Hotspot probes (GRID)
  2. COMFA

Kanishk

Shyam

Goodford001.pdf

Kubinyi002.pdf

Bunce001.pdf

2006.11.20

Mon

Discovery Methods Applications

  1. Human Carbonic Anhydrase
  2. Estrogen Receptor

Aniel

Priya

Klebe001.pdf

Waszk001.pdf

Tamoxifen001.pdf

         

2006.11.22

Wed

 

** Quiz Prior Section IV **

SECTION V:
LEAD REFINEMENT

Free Energy Perturbation (FEP)

  1. Thermolysin with 2 ligands

Vadim

Kollman009.pdf

Jorgensen006.pdf

Kollman007.pdf

2006.11.27

Mon

Linear Response

  1. Intro to Linear Response (LR method)
  2. Inhibition of protein kinases (Extended LR method)

Lakshmi

Sarah

Aqvist001.pdf

Jorgensen001.pdf

Aqvist002.pdf

rizzo008.pdf

2006.11.29

Wed

MM-PBSA, MM-GBSA

  1. Intro to Molecular Mechanics Poisson-Boltzmann / Generalized Born Surface Area Methods
  2. MM-PBSA Validation Study

Rose

Freda

Kollman012.pdf

Kuhn001.pdf

 

2006.12.04

Mon

MM-PBSA, MM-GBSA.

  1. Example: gp41
  2. Example: MMPs

Dr. Ben Strockbine

(guest lecture)

Noel Carrasscal

(guest lecture)

Strockbine001.pdf

rizzo010.pdf

 

2006.12.06

Wed

Guest Lecture

  1. Working in the Pharmaceutical Industry

Dr. Elizabeth Buck

(guest lecture)

OSI Pharmaceuticals

 

 

2006.12.11

Mon

Properties of Known Drugs

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

Jeremiah

Suzanne

 

Murcko001.pdf

Murcko002.pdf

Lipinski002.pdf

Lipinski001.pdf

         

2006.12.13

Wed

Property Prediction

  1. ADME: Blood-Brain-Barrier (BBB)

 

** Quiz Prior Section V **

 

Yan

Xu001.pdf

Guttendorf001.pdf

Young001.pdf

Xu003.pdf