Macromolecular 3D Structure Visualization & Structural Bioinformatics
Amherst College, Amherst MA USA
Webster 102 Technology Classroom
9:00 AM - 12:30 PM, 1:30 PM - 5:00 PM, Saturday March 10, 2007.

Thanks to Richard Goldsby for initiating this course, and to Colleen Keenan for IT support.
Lead Instructor: Eric Martz, Ph.D.
Main author of FirstGlance in Jmol and Protein Explorer - Prof. Emeritus, Univ. Mass. Amherst; emartz@microbio.umass.edu
Co-Instructor: Frieda S. Reichsman, Ph.D., MoleculesInMotion.Com
This document is on-line: At proteinexplorer.org click on Workshops, or
http://workshops.proteinexplorer.org/amcol07.htm

Rationale & Goals: In this day of exploding bioinformatics information from genomics and proteomics, it is ever more important to be conversant with macromolecular three-dimensional structure, and how it relates to protein and nucleic acid function and drug design. This workshop will introduce participants to finding published macromolecular structure data, and visualizing and interpreting 3D macromolecular structure using state of the art, free software. Structural bioinformatics servers will be introduced that yield a wide range of types of key information, yet are easy to use. Authoring tools that facilitate preparation of interactive macromolecular structure presentations, such as those at MolSlides.Org, will be demonstrated.

Software: The central tools for this workshop (all free) are:
FirstGlance in Jmol (firstglance.jmol.org)
and Jmol java applet
  • Operates in all popular browsers and platforms, including Windows, OSX, and linux.
  • Operates on-line only.
  • Open source.
  • Assumes that you are already familiar with basic principles of protein structure.

    Exceptional ease of use. Limited set of "canned" views.

    Adopted by Nature Structural and Molecular Biology and other bioinformatics resources.
    Built upon the free, open source Jmol java applet.
    Protein Explorer in Chime (www.proteinexplorer.org).
    and Chime plugin
  • Operation limited to Windows (including on Intel Mac OS X).
  • Operates on-line or off-line (downloaded).
  • Open source.
  • Much more powerful than FirstGlance: fully customizable images with surfaces. Extensive help and reference materials useful to both students and researchers. Helps you understand and interpret. Won the 2003 MERLOT Classic Award in Biology for exemplary online learning resources: "The Protein Explorer has revolutionized the teaching of biology at a molecular level". Able to build MolSlides. Adopted by numerous bioinformatics resources. Built upon the free MDL Chime plugin (source code not open).

    Level & Pace: This workshop is designed for graduate students and researchers familiar with basic biochemistry, but with no previous molecular visualization software experience. It progresses rapidly to powerful tools that will be of interest to specialists in protein structure and bioinformatics. Experienced participants are encouraged to work at their own speed, ahead of the group -- there is plenty of power to discover within these tools!
      Laptop Computers:   Amherst College Network Connection Instructions

      Molecular Visualization Software:

      In Web Browsers:
    1. Jmol java applet (nothing to install except java, works in all popular browsers, Windows & Mac OS X):
          How to Use Jmol.     Jmol.Org     Sites Using Jmol (growing rapidly!)     Free, open source.
          User interface "wrapper": FirstGlance in Jmol: firstglance.jmol.org     Free, open source.
    2. Chime browser plugin (Windows only! Requires installation):
          How to Use Chime.     About Chime.     Free, proprietary source, development stalled since 1998.
          User interface "wrapper": Protein Explorer (requires Chime): proteinexplorer.org     Free, open source.
    3. Others..

      Stand-Alone:
    4. PyMol (pymol.sourceforge.net): Popular with crystallographers because of its power and gorgeous publication-quality images. User friendliness: poor. Documentation: not up to date. Not free (except for teaching); open source.
    5. RasMol: Best available from 1993-1997 and still widely used. User friendliness: poor (but see user interface RasTop). Documentation: good. Free and open source.
    6. DeepView also known as Swiss PDB-Viewer: Powerful modeling capabilities (see Molecular Modeling below). User friendliness: poor. Documentation: good. Free but proprietary source.
    7. Protein Workshop (java applet, visualization option at the Protein Data Bank): Beautiful images, slow performance. Ease of use: moderate. Documentation: so so. Free; source?
    8. Many others: home pages. Comparison of Protein Explorer, Cn3D, DeepView: Martz, 2003.

      Review of Protein Chemistry and Structure.

    9. Central Dogma: DNA mRNA Protein.     DNA structure in Jmol
    10. 20 Amino acids
    11. Polypeptide chain geometry and steric restrictions
    12. Covalent and non-covalent chemical bonds
    13. Secondary Structure
    14. Folding: hydrophobic collapse
    15. Protein folds cannot be reliably predicted from theory

      FirstGlance in Jmol for Simple Visualization

    16. At firstglance.jmol.org, enter 1PGB (a Protein Data Bank identification code). Try these controls:
      1. Introduction
      2. and
      3. Top 2 rows of views
      4. Vines
      5. Buttons
      6. Center Atom
      7. Reset
      8. More Views
        • Cation-pi interactions and salt bridges (1AXI, 1M4U PQS for inter-chain)
        • Distances
        • Color by uncertainty
    17. Explore 1HHO in firstglance.jmol.org, especially:
      1. Ligands button
      2. for full names of ligands
      3. Hide
      4. Find (explain the distributions of gly, pro, ala, glu, phe, viewed one at a time)
      5. Contacts to HEM
    18. 1BKX: More Views, Non-standard amino acids
    19. 2ACE:

      Introduction to Structural Bioinformatics

    20. Slides Covering:     (from bioinformatics.proteinexplorer.org)
      Finding published molecules of interest:

    21. Browsing Molecules
    22. Searching for Molecules
      Structural Bioinformatics Servers with High Value and Ease of Use:

    23. Identifying Functional Sites & Seeing Protein Evolution:
    24. Orientations of Proteins in Membranes. E. coli Porin 1HXX

    25. All-Atom Contact Analysis (clash scores with hydrogens, model quality): MolProbity. (1CBX)

    26. Generate publication quality images easily with Polyview-3D.

    27. Save any molecule you see!
      Jmol in Scientific Journals:

    28. FirstGlance in Jmol: Nature Structural and Molecular Biology

    29. "Jmolized" Figures: ACS Chemical Biology
      Protein Explorer (more help for beginners than FirstGlance) & MolSlides:

      Use Firefox (or Netscape 7.2 or Mozilla).
      • Internet Explorer cannot save MolSlides, and usually cannot display the Features of the Molecule control panel in Protein Explorer.
      • Netscape 4.8 cannot save MolSlides, but does everything else in Protein Explorer, and it works with older Chime-based websites.
      • Netscape 8 does not work with Protein Explorer.
      Go to ProteinExplorer.Org

    30. Protein Explorer     proteinexplorer.org     (8 years of Eric's work!)
      1. FrontDoor (About Protein)
      2. FirstView (explanation of backbone traces, ...)
      3. Features of the Molecule (1E3Q): Resolution, R, Rfree
      4. QuickViews for Custom Views
      5. Help/Index/Glossary: help.proteinexplorer.org

    31. What Are MolSlides?
      1. View MolSlide Examples: molslides.proteinexplorer.org
      2. Demonstration: Making MolSlides in Jmol     (Procedure)
      3. Importing and Adapting MolSlides

      Educational Resources

    32. BioMolecular Explorer 3D: Molecules for High School

    33. MolviZ.Org: Martz Central: Resources for High School, College, and Researchers.
      Bird Flu: N1 vs. Tamiflu Lesson Plan:
    34. MolVisIndex.Org: World Index of Molecular Visualization Resources
    35. Animations / Morphs: Conformational Changes

      Molecular Modeling (Time Permitting, or Later Private Sessions)

    36. Mutating your model:
      1. Changing residue sidechains and rotamer minimization with DeepView
      2. DeepView beginners should start with the superb Molecular Modeling for Beginners by Gale Rhodes, Univ. Southern Maine.
      3. DeepView resources are indexed at molvisindex.org.

    37. Aligning two or more chains or molecules, and how to view the alignment.
      1. The CE site cl.sdsc.edu/ce.html will align any two protein chains quickly and easily (but hetero atoms are discarded, and its database has not been updated since 2001).
      2. DeepView www.expasy.ch/spdbv/mainpage.html can align anything (one or more than one chains), selecting any subset of atoms for the alignment (other atoms following), and retaining hetero atoms. The results can be saved as a PDB file, but will need manual editing to separate models with MODEL [N] and ENDMDL records so that Protein Explorer can distinguish the models. Gale Rhodes provides a DeepView tutorial: click on the section Comparing Proteins.

    38. Homology (comparative) modeling: Introduction.


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