[Chimera-users] viewing & comparison of multiple overlay structures

[Roberta King]

Thank you Eric for your very detailed answers to my several questions. It
will take me a few days to work through the suggestions. If I have any more
troubles, I will contact you next week.

 

Thanks very much,

Roberta King

 

********************************

Roberta S. King, Ph.D.

Department of Biomedical and Pharmaceutical Sciences

College of Pharmacy

University of Rhode Island

http://www.uri.edu/pharmacy/faculty/king

 

  _____  

From: Eric Pettersen [mailto:pett at cgl.ucsf.edu] 
Sent: Tuesday, April 03, 2007 7:57 PM
To: Roberta King
Cc: Chimera BB
Subject: Re: [Chimera-users] viewing & comparison of multiple overlay
structures

 

On Apr 3, 2007, at 1:47 PM, Roberta King wrote:

First, After overlaying multiple protein (pdb) structures with ligands using
MultiAlign based on alignment, how does one easily view only the overlaid
ligands? [Note: I have up to 36 structures overlaid, each with 0-2 ligands.]

Hi Roberta,

            Using the command line (Favorites->Command Line), typing "~disp;
show ligand" will hide all structures and then show only the ligands. If
every structure had a ligand you would only need "show ligand" since the
show command hides parts of structures that aren't to be shown, but if no
part of a structure matches the show criteria, the structure isn't changed
-- so you need the "~disp" also to guarantee that ligand-less structures get
hidden.

            This is also doable with the menus by Select->Structure->ligand
followed by Select->Invert Selection (or shift-right-arrow instead to invert
the selection in all models) and then Actions->Atoms/Bonds->hide.

            From there, you will probably want to select the ligand clump by
control dragging the mouse across the clump (there will be a green box
outline as you drag the mouse) and then use Actions->Focus to zoom in on the
clump and make it the center of rotation.

Secondly, can chimera then calculate a solvent-accessible closed surface for
the protein cavity surrounding each ligand? Alternatively, I could calculate
the cavity first, then overlay based on alignment. The goal is to view the
overlaid cavities for visual comparison.

            It depends. If the cavity is actually completely enclosed then
Chimera won't depict it. If there is some channel to the binding pocket,
then it should be depicted. I say "should" because the surfacing library we
are currently using (MSMS) is known to have problems when there are narrow
channels in a surface. We are working on a replacement library that should
solve both these problems, but it's not ready yet. Providing that MSMS
doesn't fail, your pockets should be depicted. It is also sometimes possible
to work around the MSMS problem by adding hydrogens to a structure or by
slightly changing VDW radii (with the vdwdefine command) -- but you have to
do this before any surfaces fail because after a failure surfacing won't
work again until you restart Chimera.

            You create a surface with Actions->Surface->show or the "surf"
command. If with experience you know that surfacing certain models is
problematic, you can restrict the surfacing to particular models by
selecting them before using the menus or providing the model numbers as
arguments to the surf command (e.g. "surf #0,3-7,9"). 

Thirdly, can chimera calculate electrostatic charge on amino acids
surrounding a binding cavity and reflect that charge onto the closed cavity
surface? Can this surface be included in overlay view?

            You can use the Add Charge tool (in the Structure Editing
category) to add partial charges to all atoms. You can then use the Render
By Attribute tool (Structure Analysis category) to color the surface and/or
atoms based on the partial charges.

            For more precise electrostatics, you can use an external tool
such as APBS or Delphi to generate an electrostatic grid, and open that in
Chimera and then use the Electrostatic Surface Coloring tool
(Surface/Binding Analysis category) to color the surface with the grid data.

            You can certainly show the surface(s) with the ligands overlaid.
You would probably only want to show a few surfaces at most simultaneously
for understandability (see next answer).

Given the number of structures, I would much appreciate any advice on how to
make this manageable. If Chimera cannot do the calculations, can it import
multiple structures saved by another capable software, then overlay them
using MultiAlign (including the surfaces)?

            Depending on the speed of your computer, its amount of memory
and its graphics card, working with 36 structures and their surfaces at once
may or may not be satisfactory (and unless you have a real high-end machine
my guess would be not). You will want to use the Model Panel (under
Favorites) to control which surfaces/structures are being shown --
particularly which surfaces since I imagine that looking at more than a few
would be incredibly confusing.

            Another thing that will help is to delete parts of structures
that you aren't interested in. One trick here is to use MultAlign Viewer to
select one residue in each structure (create a region by mouse dragging that
covers one column in the alignment -- those residues will be selected), then
select the corresponding chains by clicking into the main window and hitting
the up-arrow key, then right-arrow to invert the selection, and finally
Actions->Atoms/Bonds->delete to delete all atoms that are not part of chains
in the alignment. Hopefully your ligands will have the same chain ID as the
chain in the alignment and therefore will not be deleted. You might want to
look at your ligands after you've inverted the selection and make sure none
are selected for the following deletion. If some are selected, deselect them
with "~select ligand".

            As a quasi-extreme measure you could prune away parts of the
structure more than a certain distance from the ligands. Select the ligand
clump and use Select->Zone... to select residues further than a certain
distance from the clump and then delete the selected residues.

 

--Eric

 

Eric Pettersen

UCSF Computer Graphics Lab

pett at cgl.ucsf.edu

http://www.cgl.ucsf.edu

 

 

 

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