Biochemistry 399, Summer 1998

A laboratory course in Computational Biochemistry for Upper Division Biochemistry Students

Organization: This laboratory course will include formal lectures and tutorials (detailed below) to present necessary concepts. Much of the class material, including all lectures will be available to enrolled students on the World-Wide-Web. Lab reports will be created as Web documents using simple convenient tools available on the student workstations.

Grades: The students grade will be based on his or her Web-reports (8) and a final exam.

Course Outline (designed for 26, 75 minute periods)

• Introduction to UNIX based Graphics Workstations (tutorial: 1 period)
  • orientation- student accounts/ disk space/class directories/ e-mail
  • contrast between UNIX and DOS- managing files and directories
  • contrast between SGI Windows interface and MAC and PC windows interfaces - mouse buttons, multitasking, disk & directory access paths
  • using unix software
  • using network software (FTP, Telnet and Netscape)
• Laboratory (1 period): familiarization with the workstation, file transfer and unix software.

• Lecture - A review of fundamentals of protein structure. (1 period)
• Browsing the Web -- structure biology and computational chemistry resources on the Web (tutorial: 1/2 period)
• A detailed look at the Web based Protein Data Bank (PDB) of over 4000 macromolecular structures. (tutorial: 1/2 period)
  • What's in a PDB file?
  • Displaying structures on the Workstation AND on a PC
  • Molecular graphics on a Workstation AND on a PC
• Lecture/tutorial - creating lab reports using SGI's Webmagic, xv and RASMOL (1 period)
• Laboratory exercise (1 period):
  • Students will examine an assigned protein in detail using the RASMOL molecular graphics software to
    • generate ribbon diagrams of the folding
    • highlight and color encode unique or unusual substructure
    • calculate and display secondary structure components
    • correlate secondary structure and hydrogen bonding patterns
• Lecture (1 period) : Atom sizes, surfaces and volumes..the information they provide about buried residues, solvation energy, etc.
• Laboratory exercise (1 period):
  • Students will calculate the surface and volume of their protein, evaluate the surface exposure of the amino acid residues and plot a graph of fraction buried versus amino acid (this item is tentative, subject to finding an appropriate, affordable & user-friendly software package).
• Tutorial: from molecular graphics (RASMOL) to molecular modeling (SYBYL) (1 period)
• Laboratory exercise (1 period):
  • Students will then compare their assigned structure to one or more structures of homologous proteins to define
    • how sequence differences and structure differences compare (using color coded graphics and numerical analysis)
    • how to quantify structure comparisons (RMS calculations and torsional maps)
• Lecture - What the PDB teaches us about Protein Structure... (1 period)
• Laboratory exercise (2 periods):
  • Students will use the tools they've acquired to analyze the structural changes associated with either a protein-protein or a protein-ligand interaction.

MOLECULAR MECHANICS SECTION: (10 class periods)

• Lecture - The fundamentals of macromolecule molecular mechanics (1 period)
• A close look at the SYBYL force field - (Tutorial: 1 period)
  • Equations used
  • Parameters
  • Options and what they mean
• Laboratory exercise (1 period):
  • Students will use molecular mechanics to refine a small molecule structure that they create "free-hand" then compare it to the crystal structure from the small molecule database (Cambridge).
• Lecture - The fundamentals of macromolecule molecular mechanics #2 (1 period)
• Laboratory exercise/tutorial (1 period):
  • Groups of students will used different force field options to minimize a set of strained alpha-helix models to see which form of the force field converges best.
• Lecture - Modeling protein structure by homology (1 period)
• Laboratory exercise (1 period):
  • Students will do a simple homology modeling exercise, taking a sequence of a homologous protein, changing a known structure to match it and then minimizing to get a model of the structure which will then be compared to the known structure of the homolog.
• Lecture - The water problem. Modeling a mixed dielectric environment (1 period)

MOLECULAR DYNAMICS SECTION (7 periods):

• Lecture - Fundamental concepts of molecular dynamics (1 period)
• Tutorial - Demonstration of using Sybyl to do MD calculations (1 period)
• Laboratory exercise (2 periods)
  • Students will minimize a small peptide structure and prepare it for MD. They will warm it in stages and carry out a short MD run.
• Lecture - Analysis of an MD data set (1 period).
• Laboratory exercise (1 period)
  • Students will generate and analyze some trajectories from their simulations and continue preparation of their final report on the MD studies.