Date : January 13, 2003

BIOL 952: Introduction to Molecular Modeling

instructor: Krzysztof Kuczera, 5088 Malott, 864-5060, kkuczera@ku.edu

semester: Spring 2003

time & place : TR 8:30-9:20, Room 2025 Haworth

line # : 17625          Credit hours : 3

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The course consists of three parts: a "theoretical" lecture, a "laboratory" lecture and a computer laboratory. The lectures will be held in class. The computer laboratory part will be performed in small groups on computers at several sites on campus. The instructor and/or other qualified personnel will be available for consultation during laboratory hours and at other times as needed. Gerald Lushington, the Director of the Molecular Graphics and Modeling Laboratory, will be elping with the quantum chemistry module.

The goal of the course is to introduce students to computing and molecular modeling techniques so that they will be able to perform standard computational tasks as part of their research. There is no official textbook; the book by A. R. Leach is recommended. Some useful references are given below. There will be no separate exams in the class. The evaluation of performance will be based on laboratory reports, consisting of descriptions of methods, goals and results from the computer laboratory exercises, and a presentation based on on a modeling article from the literature.

The whole class is organized around a central Web site, at

    http://pekoe.chem.ukans.edu/~kuczera/Public/web/html/molmod.html

This site will contain all course materials : theoretical and laboratory lecture notes, tutorials for major software, manuals for computer laboratory exercises, modeling case studies as well as a mini-manual for UNIX.

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THEORETICAL LECTURE

1. Introduction. Modeling with potentials (2 sessions).
2. Molecular mechanics. Describing molecules; Force fields : intra- and intermolecular terms; Algorithms : energy evaluation & minimization, conformational search, docking, constraints, molecular vibrations. (5 sessions).
3. Molecular dynamics. Basic algorithms; Trajectory analysis; Applications; Special algorithms - boundaries, constraints, constant P,T etc. (5 sessions)
4. Molecular modeling. Using bioinformatics databases; Basic macromolecular structure analysis; Sequence alignment; Homology modeling; Docking; (5 sessions)
5. Special topics. Limitations and future trends. QM/MM methods. Data analysis. Quantum chemistry. (3-5 sessions)
6. Student seminar. Students present brief seminar based on a selected published article. (2-3 sessions)

LABORATORY LECTURE

1. Introduction to UNIX, computer workstations, networking and the WWW
2. BIOLAB: Introduction to modeling software
3. QUANTA/CHARMM : describing molecules
4. The Brookhaven Protein Data Bank
5. Cambridge Structural Database
6. QUANTA/CHARMM : structural and energetic dictionaries
7. QUANTA/CHARMM : calculating energy
8. QUANTA/CHARMM : energy minimization
9. QUANTA/CHARMM : molecular vibrations
10. QUANTA/CHARMM : manipulating molecules
11. QUANTA/CHARMM: Conformational search
12. AutoDock, DOCK, FTDOCK: Docking
13. LIGPLOT, NACCESS, HBPLUS: structure analysis
14. MODELLER: sequence alignment and homology modeling
15. CHARMM : molecular dynamics
16. CHARMM : solvation
17. Introduction to GAUSSIAN.
18. Optional: Special topics depending on interest of students and available time (e.g. QM/MM, computational spectroscopy, data analysis, Mathematica, ...)

COMPUTER LABORATORY

GENERAL INTRODUCTION: BIOLAB

0

Setting up computer accounts, lab groups and workstations (Week 1)

1

Introduction to UNIX and SYBYL program (Week 2)

2

Exploring the Protein Data Bank (Week 3)

3

RasMol and MolScript (Week 4)

4

Molecular graphics for screen, paper and Web (Week 5)

5

Molecular energy surfaces with QUANTA/CHARMM (Week 6)

6

Introduction to GAUSSIAN (Week 7)

COMPUTATIONAL BIOCHEMISTRY TRACK: COBLAB

7A

Normal mode analysis : water (Week 8)

8A

Conformational search : energy minimization (Week 9)

9A

Conformational search : molecular dynamics (Week 10)

10A

MD simulation of a small protein : BPTI in vacuum (Week 11)

11A

QM/MM simulation of enzymatic reaction (Weeks 12-13)

12A

Individual student-generated projects (Weeks 14-15).

MOLECULAR MODELING TRACK: MODLAB

7B

Bioinformatics: using the Web and the Cambridge Structural Database (Week 8)

8B

LIGPLOT, NACCESS, HBPLUS : analyzing macromolecular structures (Week 9)

9B

AutoDock and DOCK: docking (Week 10)

10B

MODELLER: sequence alignment (Week 11)

11B

MODELLER: homology modeling (Week 12-13)

12B

Individual student-generated projects (Weeks 14-15).

LITERATURE (in order of usefulness)

1. A. R. Leach, Molecular Modeling. Principles and Applications, Addison Wesley Longman, 1996.

2. A. K. Rappe and C. J. Casewit, Molecular Mechanics Across Chemistry, University Science Books, 1997.

3. M. Karplus, G.A. Petsko, Molecular dynamics simulations in biology, Nature,347,631-639 (1990).

4. W.F. van Gunsteren and H.J.C. Berendsen, Computer Simulations of Molecular Dynamics: Methodology, Applications and Perspectives in Chemistry, Angew. Chem. Int. Ed. Engl., 29, 992-1023, 1990.

5. C.L. Brooks III, M. Karplus, B.M. Pettitt, Proteins: A Theoretical Perspective of Dynamics, Structure, and Thermodynamics, John Wiley and Sons, New York, 1988.

6. J.A. McCammon and S.C. Harvey, Dynamics of Proteins and Nucleic Acids, Cambridge University Press, 1988.

7. G. Todino, J. Strang and J. Peek, Learning the UNIX operating system, 3rd Ed, O'Reilly & Associates, 1993.

8. J. M. Haile, Molecular Dynamics Simulation. Elementary Methods, John Wiley and Sons, New York, 1992.

9. Allen & Tildesley, Computer Simulations of Liquids, Clarendon, Oxford, 1987.