Date:  January 12, 2009

 

BIOL 952:  Introduction to Molecular Modeling

 

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

Semester:  Spring 2009

Time & place :  TR 8: 30–9: 20, Room 2025 Haworth

Line #  :  83165           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 two-part computer laboratory will be performed in small groups on UNIX computers in the MGM Laboratory. The first part of the lab is a set of introductory exercises to be taken by all students.  The second part contains specialized projects in three "tracks", designed for students with biological, chemical and chemical engineering interests. The instructor and/or other qualified personnel will be available for consultation during laboratory hours and at other times as needed.

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: //oolung.chem.ku.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.

 

THEORETICAL LECTURE (outline)

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. (5-6 sessions).

3.    Molecular dynamics and Monte Carlo methods. Basic algorithms; Trajectory analysis; Applications; Special algorithms – boundaries, constraints, constant P,T, statistical mechanics. (5-6 sessions)

4.    Molecular modeling. Using bioinformatics databases; Basic macromolecular structure analysis; Sequence alignment; Homology modeling and threading; Docking; (5-6 sessions)

5.    Quantum chemistry. (2-3 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.  Gaussian:  energy, optimization, vibrations

18.  Gaussian:  binding energies and transition states

19.  MCCCS:  advanced statistical mechanics

 

 

 

COMPUTER LABORATORY

 

GENERAL INTRODUCTION 

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     Open or Introduction to GAUSSIAN (Week 7)

 

COMPUTATIONAL BIOCHEMISTRY TRACK:  A

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   MD simulation of solvated peptide (Weeks 12-13)

12A   Individual student-generated projects (Weeks 14–15).

 

MOLECULAR MODELING TRACK:  B

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).

 

CHEMICAL ENGINEERING TRACK:  C

7C  Thermodynamics:  vapor-liquid equilibria (Week 8)

8C  Thermodynamics:  alkane adsorbtion on zeolites (Week 9)

9C  Kinetics:  transport coefficients in solution ( Week 10)

10C   Quantum chemistry:  basic electronic structure calculations - part 2 (Week 11)

11C   Quantum chemistry:  ligand binding to catalyst (Week 12-13)

12C   Individual student-generated projects (Weeks 14–15).

 

 

 

LITERATURE (in order of usefulness)

 

1.    A. R. Leach, Molecular Modeling.  Principles and Applications, Pearson Education Ltd., 2nd Ed., 2001.

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, OÕReilly & 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.

10.  Frenkel & Smit, Understanding Molecular Simulation, Academic Press, San Diego, 1996.