CPSC 689 - Structural Bioinformatics
Professor: Dr. Thomas R. Ioerger
Office: 322C Bright Bldg (or 218 BioBio)
Phone: 845-0161 (or 862-7636)
email: ioerger@cs.tamu.edu
Meeting: MF, 9:00-10:30, 106 BioBio
Textbook: Molecular Modeling and Simulation, Tamar Schlick, 2002.
available online through TAMU libcat
Goals of the Course: The course will cover various aspects of
protein structure analysis, with a focus on computational methods for
modeling, simulation, and prediction.
Syllabus:
- Review of protein structure
- Interatomic forces
- Folding (thermodynamics and kinetics)
- Fold recognition
- Homology modeling
- Dynamics, flexibility, and normal modes
- Protein-protein interactions
- Molecular mechanics forces fields
- Minimization
- Molecular dynamics
- Electrostatics (Poisson-Boltmann)
- Solvation energy (Generalized-Born)
- Protein-ligand interactions (forces, kinetics)
- Docking, virtual screening
Schedule
Wed, Jan 21: first day of class (9:10-10:100, 203 Bright)
Fri, Jan 23: background - amino acids, side-chain properties (9:00-10:00, 106 BioBio)
Mon, Jan 26: peptide bond, phi/psi angles, rotamers
Thurs, Jan, 29: secondary structures
Fri, Jan, 30: sec. struct. preduction, trans-mem and signal peptides, disordered regions
Mon, Feb 2: domains, fold classes, structure superposition algorithms
Fri, Feb 6: fold recognition methods
Mon, Feb 9: forces governing folding (electrostatic, VDW, H-bonds, pi-pi...)
Wed, Feb 11: special class to discuss project ideas for those taking it for credit
Fri, Feb 13: more forces...
Mon, Feb 16: surfaces, MS vs. SAS, density/packing in core
Fri, Feb 20: protein-protein interfaces;
Mon, Feb 23: Homology Modeling, sequence alignment
Fri, Feb 27: Modeller (spatial restraints), threading, loops, pairwise-contact PDF's
Mon, Mar 2: Protein Folding (time scales, cooperativity, Levinthal paradox)
Fri, Mar 6:
Mon, Mar 9:
Fri, Mar 13:
Mar 16-20: Spring Break
Mon, Mar 23: electrostatics - PB equation, Delphi
Fri, Mar 27: (class cancelled - ABCS Workshop)
Mon, Mar 30: (class cancelled - technical problems)
Fri, Mar 13: using Delphi - demo
Mon, Apr 6: solvation energy - using Delphi, Generalized Born model
Fri, Apr 10: force fields
Mon, Apr 13: Gasteiger charges; minimization methods
Fri, Apr 17: molecular dynamics - solving equations of motion
Mon, Apr 20: CHARMM
Fri, Apr 24: implicit and explicit solvent simulations
Mon, Apr 27: Dobbins, Lesk, and Sternberg (2008), Tama and Sanejouand (2001) normal modes analysis (Lantao)
Fri, May 1: Derreumaux and Shlick (1998) loop opening in triose phosphate isomerase (Wan Wen)
Mon, May 4: Ma and Nussinov (2003) unfolding of micro-globulin (Cindy)
Wed, May 6: Trevino, Scholtz, and Pace (2007) effect of mutations on solutbility of RNase (Joseph)
Fri, May 8: Hensch and Tidor (1994) salt bridges and stability (Ed)
Mon, May 11: Wriggers and Schulten (1998) kinesin (Vineet)
Wed, May 13: Betts and Sternberg (1999) induced-fit in protein complexes (Yicheng)
Fri, May 15: Jackson and Fersht (1991) 2-state folding of chymotrypsin (Jean)
Slides
Resources/Links
- Anatomy and Taxonomy of Protein Structure, Jane Richardson, 1981
- PDBSelect, 25% threshold, September, 2008
- Delphi resources
- Delphi manual - good examples of how to use Delphi to compute solvation energies, pKa shifts towards bottom
- Delphi online notes from Scripps - explanation of different energy component terms (we don't have the menu-driven interface, just the standalone command line version)
- Delphi Worshop tutorial - example calculation of barnase/barstar interaction energy
- files you will need in ~ioerger/delphi on hammerhead: delphi.sh, delphi.in, parseres.crg, parseres.siz
- add all H's with sybyl8.0; remove all ligands/solvent
- CHARMM resources
References/Papers