Biology 5476: Modeling Biomolecular Systems I Fall 2008 Class Meetings: Tuesday and Thursday, Lecture, 1:30-3:00, CCB Classroom Friday, Laboratory, 2:00-4:00, CCB Teaching Laboratory Coursemaster: Jay Ponder (CCB 208, 362-4195, ponder@dasher.wustl.edu) Course TA: Tim Williamson (CCB 114, Pappu Lab, tewillia@artsci.wustl.edu) Web Site: http://dasher.wustl.edu/bio5476/ Overall Objective: This course covers basic computer modeling and physical simulation techniques applied to biomolecular structure and function. Laboratory sessions will expose the student to a variety of methods actively being used in current research. Suggested Texts: There are no required textbooks. The books listed below may be useful for parts of the course, and are available from online booksellers: Molecular Modeling: Principles and Applications, 2nd Ed., Leach, 2001 Understanding Molecular Simulation, 2nd Ed., Frenkel and Smit, 2002 Computer Simulation of Liquids, Allen and Tildesley, 1987 Simulating the Physical World, Berendsen, 2007 Introduction to Computational Chemistry, Jensen, 2007 Other Info: Bio 5476 is required by the Graduate Program in Computational Biology. Knowledge of basic computer use, such as file editing and the ability to manipulate data via simple shell scripts is assumed. Some prior background in physical chemistry is highly recommended prior to enrollment, but is not required. Grades will be based on laboratory write-ups and a take-home final exam to be distributed the last week of the course. Module 1: Empirical Force Fields & Quantum Mechanics Aug 28 Molecular Mechanics Energy Functions Ponder Sep 2 Electrostatics and Polarization for MM Ponder Sep 4 Potential Surfaces and Optimization Methods Ponder Sep 5 Laboratory (Conformational Analysis) Ponder Sep 9 Basics of Molecular Orbital Theory Ponder Sep 11 User's Guide to QM Methods Ponder Sep 12 Laboratory (Protein Molecular Dynamics) Ponder Module 2: Monte Carlo & Molecular Dynamics Simulations Sep 16 Monte Carlo Techniques Ponder Sep 18 Molecular Dynamics Techniques Ponder Sep 19 Laboratory (Computing Properties of Liquids) Ponder Sep 23 Computation of Properties from Simulation Ponder Sep 25 Path Methods for Navigating Potential Surfaces Ponder Sep 26 Laboratory (Trypsin/Benzamidine Complex) Ponder Module 3: Electrostatics & Solvation Sep 30 Electrostatics & Solvation I Baker Oct 2 Electrostatics & Solvation II Baker Oct 3 Laboratory (Introduction to APBS) Baker Oct 7 Electrostatics & Solvation III Baker Oct 9 Electrostatics & Solvation IV Baker Oct 10 No Class Ð DBBS Biochemistry/Biophysics Retreat Oct 14 Electrostatics & Solvation V Baker Module 4: Free Energy Methods, Docking & Binding Oct 16 Brownian Dynamics & Kinetics I Sept Oct 17 No Class Ð Fall Break Oct 21 Brownian Dynamics & Kinetics II Sept Oct 23 Free Energy Methods I Sept Oct 24 Laboratory Sept Oct 28 Free Energy Methods II Sept Oct 30 Docking & Binding Sept Oct 31 Laboratory Sept Module 5: Cheminformatics & Drug Discovery Nov 4 QSAR and 3-D QSAR Marshall Nov 6 Pharmacophore Active Site Modeling Marshall Nov 7 Laboratory (3D QSAR) Marshall Nov 11 Structure-Based Drug Design Marshall Nov 13 Chemoinformatics Marshall Nov 14 Laboratory (Virtual Screening) Marshall Module 6: Homology Modeling, Structure Prediction & Design Nov 18 Template-Based Modeling of Protein Structure Marshall Nov 20 Molecular Recognition: The DevilÕs in the Details! Marshall Nov 21 Laboratory (Ligand Refinement) Marshall Nov 25 Structure Prediction: Homology Modeling Marshall Nov 27 No Class Ð Thanksgiving Break Nov 28 No Class Ð Thanksgiving Break Dec 2 Structure Prediction: Threading Methods & ab Initio Marshall Dec 4 Structure Prediction: Design & Engineering Marshall Dec 5 Laboratory (Homology Modeling) Marshall