OUTLINE OF A COURSE IN BIOINFORMATICS

The course will introduce the basic computational issues and methods used in molecular biology and biochemical kinetics. It will introduce and use biological data sources available on the world wide web media and most popular computational programs. Topics will include basic algorithms for molecular mechanics of biomolecules and analysis of biological sequences, reaction mechanisms of enzymatic catalysis, thermodynamic and kinetic foundations, metabolic pathways. The course will provide the theoretical background for the understanding of and practical instruction for carrying out computer simulations of biopolymers. Other areas include: secondary and tertiary structure of protein, domains, families of folds, protein folding and thermodynamic stability, prediction of protein structure, modeling of antibody-antigen interactions. Interactive computer graphics programs will be used to illustrate these problems.

The course will be fine-tuned to the eventual distribution of the participants over biology, physics, mathematics and informatics.

Biochemistry of nucleic acids, proteins and carbohydrates

Fundamentals of molecular biology: gene regulation and expression

- Nucleic acid structure

- Amino acids

- Secondary structure

- Favored peptide conformations

- Domains architecture

- Where do 3D structures come from?

- NMR distance-constrained ensembles

- Crystallographic phases & electron density

- Crystallographic refinement

- Crystallography & NMR programs - CNS, X-plor

- Measure structure quality

- Visualization tools (Rasmol, VMD, SPDBV)

Basic principles and methods

- Born-Oppenheimer Approximation

- Quantum engines Molecular Orbital methods

- Semiempirical Hartree-Fock methods

- Modified Intermediate Neglect of Differential Overlap (MINDO)

- Modified Neglect of Diatomic Overlap (MNDO) - AMPAC, MOPAC

- ab initio Hartree-Fock programs - GAMESS, Gaussian

- Semiempirical engines (Molecular Mechanics) from above & spectroscopy

- Programs AMBER, Discover, CHARMM, NAMD, Insight, SYBYL, Hyperchem.

- CHARMM (Chemistry at HARvard Molecular Mechanics)

Molecular mechanics

- Atomic forces

- Energy minimization

- Molecular dynamics

- Effects of water

- Small protein molecular dynamics

- Protein simulation time scales

- 3D structure & chemical genetics

- Altered specificity mutants

- Peptide protecting groups

- Modified backbones (for stability)

- Measuring 3D protein family relationships

- "function from structure"

- Docking

- Structure based drug design