This hands-on computer workshop will enable novices to find published structures for molecules of interest, visualize the three-dimensional structures, and understand the resulting computer images. No previous experience with molecular visualization or modeling is required. QuickViews menus make it easy to highlight features such as backbone traces, disulfide bonds, secondary structure, ligands, and distribution of hydrophobic residues. Context-sensitive help is displayed automatically with each operation. Noncovalent bonds between ligands and receptors, between protein and DNA, etc. can be located easily. Clicking on any residue produces an identification report. The amino acid sequence can be displayed and clicking on residues highlights their positions in the 3D structure. Solvent-accessible surfaces can be displayed. The software is free and works on Windows and Macintoshes. Those familiar with RasMol will find Protein Explorer familiar, yet easier and more powerful.

Topics below will be demonstrated, allowing time for hands-on work. Ask questions at any time! Work at your own speed and feel free to move ahead of the group if you wish. You can have multiple sessions of PE running concurrently: if you know the PDB identification code for a molecule of interest, you may want to put it in a second session.

This is an outline, not an explanation. The explanations are built into Protein Explorer.

With "Beginner's Quick Start" (1d66):

1. What you can learn from the FirstView page.
   Basic operation of PE.
   Water, chains (how many?), ligands, disulfide bonds.
   Form for recording observations.

2. Molecule Information Window.
   PDB files, Headers, Structure Explorer, Sequences.

3. Explore More leading to QuickViews
   Buttons
   Menus SELECT, DISPLAY, COLOR

4. Secondary structure (SELECT Chains, DISPLAY Cartoon, COLOR Structure).

5. Amino and carboxy termini (COLOR N->C rainbow).

6. Temperature (COLOR Temperature).

7. Hydrophobic core (SELECT Protein, DISPLAY Spacefill, COLOR Polarity2).
   Try the [Slab] button.

8. DNA vs. RNA (SELECT Nucleic, click on "distinguish DNA from RNA").
   Try this on 104D and 1TRA.

9. DNA bases. SELECT Nucleic, DISPLAY Sticks, COLOR ACGTUbb.

10. Exploration of hydrogen bonds between DNA bases. SELECT Nucleic, DISPLAY Only, [Center], DISPLAY Stick, COLOR Element (CPK).
    1. Scroll down to QuickViews Plus, set "thickness of sticks" to 0.01 Å.
    2. DISPLAY HBonds: donor to acceptor.
    3. Find the longest hbond. SELECT Clicked: Residues.
    4. Click the two nucleotides that have the longest hbond to select them (41 atoms).
    5. DISPLAY Only.
    6. Stop selection by clicks.
    7. SELECT Inverse, DISPLAY *Hide* (hides selected hbonds).
    8. DISPLAY Clicks: Label. Click on the two visible phosphorus atoms. Change the label font size from the default 8 to 12 or 16.
    9. Change clicks to display monitor lines. What are the lengths of the longest and shortest hbonds? (7.0 and 2.6 Å).
    10. DISPLAY HBonds: backbone-trace atoms.
    11. SELECT Nucleic, DISPLAY Stick.
    12. DISPLAY HBonds: backbone-trace atoms. (Zoom -)
    13. In QuickViews Plus, change New Display to "is added to" previous display.
    14. DISPLAY Backbone.
    15. Click the red + at DISPLAY until it becomes -. DISPLAY Stick.

11. Seq3D: Highlight a range of residues.
    1. Close the PE window ("Quit"). Start another PE session with the Quick-Start for 1d66.
    2. Open Molecule Information, then Seq3D.
    3. Select "Show & select range".
    4. Click the ends defining a range in Chain A.
    5. Click on the molecule to pop QuickViews into the foreground.
    6. COLOR Red.
    7. SELECT Chain A.
    8. DISPLAY Backbone.

12. Exploring contacts to a portion of a molecule.
    1. FirstView: Reset View, then Explore More to return to QuickViews.
    2. With Seq3D, select any range of residues in either protein or DNA.
    3. Close the Seq3D and Molecule Information windows.
    4. DISPLAY Contacts.
    5. [Center], Cancel. Zoom +.
    6. Return to Contacts Help.
    7. Try out all the links in the middle frame.

13. Cation-pi interactions and salt bridges.
    1. Quit PE.
    2. At the FrontDoor, use the quick-start for "SH3 domain:peptide complex".
    3. In QuickViews, DISPLAY Cation-Pi.
    4. Click the link to CaPTURE, enter this molecule's PDB ID. (Don't know it? Use Molecule Information.)
    5. Leaving the CaPTURE window open, change back to PE.
    6. COLOR Element (CPK).
    7. [Bkg] to black background.
    8. DISPLAY Clicks: Label. Click to label each highlighted residue.
    9. Consult CaPTURE to determine which pair(s) are energetically insignificant. Can you guess why?

       Optional sequence to hide the insignificant pair:

    10. Check the box to "unlabel clicked atoms" and unlabel the energetically insignificant pair(s).
    11. SELECT Clicked: residues. Click the insignificant residues.
    12. Stop selection by clicking.
    13. Click the dot in front of the word "DISPLAY" until it changes to a red minus (-).
    14. DISPLAY Ball & Stick.
    15. COLOR Chain.

14. FrontDoor: Startup Options for Your Molecules. At the FrontDoor, you can learn about:
    1. Finding molecules with PDB Lite and other resources.
       The World Index (www.molvisindex.org) has a new category with sources of unusual molecules, including small biochemicals, organic and inorganic compounds and crystals.
    2. Finding probable quaternary structures at EBI.
    3. Aligning any two protein chains quickly and easily (Shindyalov's Combinatorial Extension server).

    4. Making hyperlinks that prespecify molecules (for your research or class website).

15. Coloring a protein by conservation-mutation from a multiple protein sequence alignment (MSA3D).
    1. At PE's FrontDoor, click the yellow and green icon at the very upper left. Click the [More] button and read all the subsequent pages. Don't miss the alignment listing.
    2. If you want to try this yourself, go to Advanced Explorer, click on MSA3D, and follow the MSA3D Tutorial.

16. The following sections of the tutorial employ techniques not yet covered. To open the tutorial, at the FrontDoor, in the right-most gray box "About PE", click Tutorial (about half-way down). To try one of the topics below, click on the numbered section link in the contents at the top of the tutorial.
    • 42. Seq3D: Scrutinizing sequence gaps.
    • 43.iii. The Noncovalent Bond Finder
    • 47. How can I see the molecule in stereo?
    • Chapter IV: Finding and Saving the Molecule of Your Choice
    • 53. Chime's Command Language.
      If you know some RasMol commands, you'll enjoy trying out PE's command alias feature (e.g. enter "s bb" to avoid typing "select backbone"). If you don't know any RasMol commands, you probably don't need to learn any to use PE.
    • 54. Multiple-model ensembles (NMR).