ConSurf in FirstGlance

What FirstGlance in Jmol can reveal
in a ConSurf or result.

Contents

What are FirstGlance in Jmol and ConSurf?
Changing from the ConSurf to the FirstGlance control panel -- and back.
Hiding and Finding portions of the molecule.
Conservation of Salt Bridges and Cation-Pi Orbital interactions.
Conservation of the contacts (non-covalent bonds) to any selected moiety.

Elsewhere:
Making presentations that show ConSurf results.
Downloading ConSurf results to save them for later display.

*Selecton:
All the above sections except 1, 6, and 8 apply to Selecton as well as to ConSurf.
In the applicable sections, please think "Selecton" wherever "ConSurf" is mentioned.

What are FirstGlance in Jmol and ConSurf?
- FirstGlance in Jmol (first available Fall, 2005) is a simple tool for visualizing 3D macromolecular structure. It works on-line, in a web browser. Nothing specific needs to be installed to use it. It is free, and an open-source project. Several scientific journals and structural bioinformatics websites provide links to FirstGlance in Jmol to make it easy for their users to see protein and nucleic acid structures. Snapshots.. Interactive Gallery.. More..
  
  Beginning with version 0.995 (August, 2006), FirstGlance in Jmol can display ConSurf results.
- ConSurf (first available Fall, 2002) is a free server that colors a 3D model of a protein molecule (PDB file) to show the evolutionary conservation of each amino acid. It does this entirely automatically, but optionally enables you to customize the process. It uses a sophisticated published algorithm, and involves gathering related protein sequences (with PSI-BLAST) from Swiss-Prot or UniProt, making a multiple sequence alignment (with MUSCLE), constructing a phylogenetic tree, and using these to calculate evolutionary conservation scores. More..
  
  From 2002 through 2006, ConSurf had only one option for viewing its results: Protein Explorer (first available Fall, 1998; obsolete by 2008). Starting in Fall 2006, FirstGlance in Jmol was added as an alternative viewer. The remainder of this document concerns the use of FirstGlance in Jmol for viewing ConSurf results.
Changing from the ConSurf to the FirstGlance control panel -- and back.
- When you view a ConSurf result in FirstGlance in Jmol, you start at a special control panel designed to show the ConSurf result. At the bottom left is a link (Explore this molecule with FirstGlance in Jmol) that enables you to change to the main control panel of FirstGlance in Jmol -- the only control panel available when looking at a protein molecule that has not been processed by ConSurf.
  
  Once you enter the main FirstGlance in Jmol control panel, there is always a link (ConSurf Controls) near the middle of the left side that takes you back. Thus, you can move freely back and forth between the two control panels.
  
  FirstGlance offers you views of the molecule (unrelated to conservation) that will help you understand the molecular structure in greater detail.
  
  Some of the views in FirstGlance can use the ConSurf colors, as an alternative to their usual colors. You can control which color scheme is used with the checkbox (ConSurf Colors) near the left middle.
Hiding and finding portions of the molecule.
- In complicated molecules with many chains, it may be useful to hide some chains to simplify examination of the conservation pattern in the chain(s) of interest. Even in single-chain molecule, it might be helpful to hide portions of the chain.
  
  A Hide.. dialog is available in the FirstGlance control panel. Here, you can hide portions of the molecule by clicking on them. The hidden portions remain hidden in all other views, including views obtained at the ConSurf control panel, until you re-enter the Hide.. dialog and explicitly re-display them (or click Reset in the FirstGlance control panel).
- A Find.. dialog is available in the FirstGlance control panel. Here, you can enter sequence numbers or other designations for specific parts of the molecule, and those parts will be highlighted with gold halos. You can see the ConSurf colors clearly inside the halos. These halos persist in all other views, including views obtained at the ConSurf control panel, until you re-enter the Find.. dialog and clear the designated parts.

Conservation of Salt Bridges and Cation-Pi Orbital interactions.

Under the Tools Tab is an option to show all salt bridges and cation-pi orbital interactions in the molecule. With a ConSurf result, these can be colored by conservation.

Variable Conserved

An energetically significant interaction (confirmed with the CaPTURE Server) between Arg 234 in the alpha chain and Tyr 10 in the beta chain of 2VAA. (Distance ~4 Å)		Arg 234 is highly conserved.

Conservation of the contacts (non-covalent bonds) to any selected moiety.

Conservation of the contacts (non-covalent bonds) to any selected moiety can easily be visualized, using the Contacts.. dialog in the FirstGlance control panel. While you select the moiety of interest (by clicking on it), the color scheme will temporarily be changed to simply color each chain differently. After you display the contacts to the selected moiety, the color scheme will automatically return to the ConSurf colors.

In the examples below, the target for the contacts display is a single chain, which happens to be colored green -- easily distinguished from any colors in the ConSurf color scheme. In other cases, the target may be an inopportune color, or may consist of many chains and so many colors. For these latter situations, a special checkbox is provided, Color Target Gray. This makes it easier to visualize the ConSurf colors in the atoms contacting the target.

Example: A major histocompatibility protein (class I, PDB code 2VAA) is one example of a ConSurf result in the FirstGlance Gallery. The contacts of the alpha chain to beta-two microglobulin are largely conserved. In contrast, the contacts of the alpha chain to the peptide bound in its groove are extremely variable (due to the large number of alleles for this gene). One exception is a highly conserved residue in the floor of the groove that interacts with the anchor residue of the peptide. Another exception is the residues at the end of the groove that interact with the carboxy termini of peptides. Of course, in FirstGlance, you can click on any residue to identify it.

Variable Conserved

Conservation of amino acids in the alpha chain that contact beta-2 microglobulin (light green chain).		Variability of the amino acids in the alpha chain groove that contact the bound peptide (green) -- but with striking conservation of a few residues.

Feedback to Eric Martz.