Structural Bioinformatics in Micbio 565
by Eric Martz
guest lecturer, Laboratory in Molecular Genetics - Steve Sandler
Dept Microbiology, University of Massachusetts (UMass), Amherst

How to find this page!
I. Introduction
II. Review of Protein Structure
III. Examples 		IV. Tools
V. Powerpoint Assignment
    I. Introduction to Structural Bioinformatics

  1. Introduction to Structural Bioinformatics includes:
    1. Why do we care about 3D macromolecular structure?
    2. What are 3D structure data?
    3. Where do 3D structure data come from?
    4. How much 3D structure knowledge do we have?
    5. Primary and Derived 3D Structure Databases

    II. Review of Protein Structure

  2. Central dogma: DNA -> RNA -> Protein
  3. 20 Amino acids
    • Codon = 3 nucleotides; 4 nucleotides3 = 64 codons.
  4. Polypeptide chain geometry and steric restrictions
  5. Covalent and non-covalent chemical bonds
    • Covalent bonds: lengths and angles nearly constant
    • Non-covalent bonds: variable lengths and angles
      • Salt bridges (up to 4.0 Å in proteins)
      • Hydrogen bonds (2.5-3.5 Å in proteins)
      • Cation-pi orbital interactions (up to 6.0 Å in proteins)
      • van der Waals interactions (up to 4.5 Å in proteins)
  6. Secondary Structure
  7. Folding: hydrophobic collapse
  8. Protein folds cannot be reliably predicted from sequence alone (using ab initio theory).

    III. Examples

  9. "The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design", Russell et al., Nature 443:45 (September 7, 2006): on-campus   off-campus
  10. Browsing for other examples:

    IV. Tools

  11. Seeing 3D protein molecules:
  12. Searching for published molecules of interest (PDB codes):
  13. Visualizing Protein Evolution:
    Animation made with Polyview-3D. Larger samples and more information...

  14. Publication-Quality Molecular Images
    • Polyview-3D is easy to use.
    • It makes beautiful static images that are ideal for scientific papers or Powerpoint.
    • It also makes animations (rotating molecules) that play in Powerpoint slides or web pages.

  15. Optional 3D Molecular Visualization Resources

    V. Powerpoint Assignment

  16. Select a personal protein molecule from one of the Browsing sites above, or by searching for a molecule of interest to you using the Searching sites below.
  17. Construct Powerpoint slides with the following contents. When completed, email your completed .ppt file to
    (Your slides need to be clear and well organized, but not polished or beautiful. They do not need to be presentation quality, but rather they are to serve as a notebook recording your work.)
  18. Technical tips: getting images and animations into Mac Powerpoint.
  19. Sample completed assignment.

    This is not a test. It is to help you learn by doing. Ask for help!

      Slide 1:
    • Your name. Your molecule's name and PDB identification code. The experimental method and resolution) (if X-ray) or number of models (if NMR).
      (For the experimental method, in FirstGlance in Jmol, click on the PDB button, then look under the Biology and Chemistry tab. Also be sure to click All Models in FirstGlance in Jmol.)
    • How many polymer chains (protein or nucleic acid chains) are in the published file at the Protein Data Bank (the asymmetric unit)?
      (If the number of chains is not obvious, in FirstGlance in Jmol, click on the PDB button, then Biology and Chemistry Tab.)
    • A snapshot of your molecule from FirstGlance in Jmol. How to take a snapshot is also linked at the bottom left (scroll down) in FirstGlance in Jmol.
      Be sure to clearly label all snapshots and animations in your slides.

      Slide 2:
    • How many polymer chains are in the "biological molecule" according to the Probable Quaternary Structure server?
      (In FirstGlance in Jmol, click on the PQS button.)
    • Side-by-side snapshots (in FirstGlance in Jmol) of the published PDB file from RCSB, and the result at PQS.
      (Even if they have the same number of chains, they may not be in the same conformation. More..)

      Slide 3:
    • 3-letter abbreviations and full names for all ligands. If none, so state.
      (In FirstGlance in Jmol, click on the PDB button, then Biology and Chemistry Tab. You can take a snapshot of the relevant lines and just paste it into a slide.)

      Slide 4:
    • A snapshot showing the Hydrophobic/Polar view of your protein.
      Is there a large hydrophobic patch? If so, show it in your snapshot. Do you think your protein is soluble? Compare it to an insoluble (transmembrane) protein, such as porin. If your protein is a membrane protein, show the snapshot from Orientations of Proteins in Membranes.

      Slide 5:
    • A snapshot showing the positive and negative charges on your protein. Use Beta FirstGlance in Jmol for this!
      Beta FirstGlance in Jmol is linked near the bottom of the main page of FirstGlance in Jmol. If there is a region of mostly positive or negative charge, show it, and suggest its function.

      Slide 6:
    • A snapshot showing some of the noncovalent bonds to one ligand or other moiety.
      Use the Contacts.. dialog of FirstGlance in Jmol. If there are no ligands, use contacts between chains, or if only one chain, contacts to a single helix or beta-strand, or to one or a few residues of special importance, such as in a catalytic site. Be sure to state what you selected as a target for the contacts in this snapshot, and make a brief comment about the contacts you show.

      Slide 7:
    • A snapshot of the ConSurf view of one protein chain in your molecule.
      If there is a highly conserved or variable region, show it in your snapshot, and suggest what its function might be.

      Slide 8:
    • An animated (rotating) view of your molecule.
      Create your animation at Polyview-3D. Use Rocking (10 degrees/step through 90 degrees) and keep the animation small (300 pixels) to prevent overloading the server! If you highlight specific residues, explain why.

* Links in this color require a Chime-compatible browser with the MDL Chime plugin installed: Thanks to Frieda Reichsman (moleculesinmotion.com) for creating some of the excellent interactive animations above.