Computational Biochemistry

Syllabus for CH588 Spring, 2001

Prerequsite: CH 561-562 or BI435 & BI440 or equivalent

Dr. Teeter (552-3615), 203 Merkert

Email: teeter@bc.edu

Useful Websites ; Homework Notes, Course Kinemages and Helper Programs

Prerequisites: CH 561-562 or BI 435 and BI 440 or equivalent

A one-semester course for chemistry and biochemistry students wishing to obtain background and experience in the molecular modeling, structural computations and molecular graphics required in biochemical research. Emphasis will be on internet access to and use of biochemical databases and molecular modeling methods.

The course will cover:

• - biochemical databases on the internet (pdb, PIR, SwissProt,...)
• - elementary UNIX commands (for SGI computer)
• - introduction and application of a programming language to reading and writing pdb files
• - brief introduction to crystallography: the data by which simulations are tested
• - theoretical instruction in molecular mechanics and molecular dynamics
• - practical experience including how to import protein crystal data, perform simulations, do conformational searches and dock molecules using the program Quanta.

The course is intended to teach the sophisticated methods required for molecular modeling in biochemical or biophysical research and to familiarize those who have not dealt with computers with these methods to gain confidence and facility in their use.

This course will include projects, exercises, problem sets, quizzes and exams. A modeling final project will be in an area of the student's choice.

Text: Computational Chemistry. Guy H. Grant and W. Graham Richards, Oxford Chemistry Primers. 1995

A Three Ring Binder is recommended.

1. a. The coordinate data file: Where to get it, what's in it and how to display it. Jan. 18-Feb 15.

• Introduction to internet and biochemical databases: how to set up browsers and retrieve files. Problem Set 1 (PS1) Internet & Kinemage.
• Protein and nucleic acid data files: The headings and crystal coordinates. How to read and write them. Simple programming.
• Programs to manipulate and display coordinates: Fortran, Kinemage and Rasmol. How to write Kinemage scripts. Problem Sets 2-4.

b. Elementary Unix commands. SGI, Insight and Quanta intro. Insight Tutorial. Problem Set 5.

2. Crystallography: A brief introduction.

3. Molecular Mechanics and validation data for each Grant and Richards: Ch. 1.

Feb. 17-March 16.

• The energy function. Grant and Richards Chapter 3.1-3.3
• Energy Minimization. Grant and Richards Chapter 3.3-3.6. Problem Set 6.
• Statistical Mechanics (Chapter 4.1-4.3) and Molecular Dynamics (Chapter 4.4-4.6). Problem Set 7.
• Modeling Biomolecules (Chapter 5)
  • Conformational Energy Searching (Quanta Manuals). Problem Set 8.
  • Homology modeling and enzyme modeling (Chapter 5. 5 - 5.5). Problem Set 9.

4. Ligand Design (Chapter 6). March. 21 - April 6.

• QSAR and Docking methods
• RMS deviation and similarity

5. Project using molecular mechanics: Start mid semester. Weekly meetings.

Project are to be chosen according to your own interests in one of the above areas. Topics will be suggested if none occur to you.

Grading: Quizzes (5%); 2 exams or 1 exam and 1 Final exam (35%); project (35%); exercises/problem sets (25%)

Quizzes are unannounced.

Study Days: May ... Final Exam: Monday ....

Websites of interest for the course:

The internet: protein/nucleic acid structural resources

• Molecular Biology Servers, Databases and Web Sites of Interest
• Protein Data Bank: Easy PDB Search
• Nucleic Acid Database

Display of structures

• Rasmol
• Kinemage

Simple Computer Programming

• Fortran: A Tutorial
• C++ Language: Tutorial 1; Tutorial 2

Molecular modeling: how to find the lowest energy conformations of biomolecules.

• Molecular Mechanics and Dynamics
• Computer Graphics in Biochemistry: A Tutorial. Tutorials are local at /km2/biochem_tutorial.

Solution of a protein crystal structure: finding the coordinates of protein that agree with crystallographic data

• Crystallography 101 - Index, a web tutorial covering many topics of this course.
• X-ray Diffraction, an overview.
• Kevin Cowtan's Picture Book of Fourier Transform

Viewing and analyzing a protein

• Web sites mentioned above are also valuable resources for this course.