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<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>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.<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'><o:p> </o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>Thanks very much,<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>Roberta King<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'><o:p> </o:p></span></font></p>
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<p class=MsoNormal><font size=3 color=navy face="Times New Roman"><span
style='font-size:12.0pt;color:navy'>********************************<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>Roberta S. King, Ph.D.<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>Department of Biomedical and
Pharmaceutical Sciences<o:p></o:p></span></font></p>
<p class=MsoNormal><st1:place w:st="on"><st1:PlaceType w:st="on"><font size=2
color=navy face=Arial><span style='font-size:10.0pt;font-family:Arial;
color:navy'>College</span></font></st1:PlaceType><font size=2 color=navy
face=Arial><span style='font-size:10.0pt;font-family:Arial;color:navy'> of <st1:PlaceName
w:st="on">Pharmacy</st1:PlaceName></span></font></st1:place><font size=2
color=navy face=Arial><span style='font-size:10.0pt;font-family:Arial;
color:navy'><o:p></o:p></span></font></p>
<p class=MsoNormal><st1:place w:st="on"><st1:PlaceType w:st="on"><font size=2
color=navy face=Arial><span style='font-size:10.0pt;font-family:Arial;
color:navy'>University</span></font></st1:PlaceType><font size=2 color=navy
face=Arial><span style='font-size:10.0pt;font-family:Arial;color:navy'> of <st1:PlaceName
w:st="on">Rhode Island</st1:PlaceName></span></font></st1:place><font size=2
color=navy face=Arial><span style='font-size:10.0pt;font-family:Arial;
color:navy'><o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'><a
href="http://www.uri.edu/pharmacy/faculty/king">http://www.uri.edu/pharmacy/faculty/king</a></span></font><font
color=navy><span style='color:navy'><o:p></o:p></span></font></p>
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<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'><o:p> </o:p></span></font></p>
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<hr size=2 width="100%" align=center tabindex=-1>
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<p class=MsoNormal><b><font size=2 face=Tahoma><span style='font-size:10.0pt;
font-family:Tahoma;font-weight:bold'>From:</span></font></b><font size=2
face=Tahoma><span style='font-size:10.0pt;font-family:Tahoma'> Eric Pettersen
[mailto:pett@cgl.ucsf.edu] <br>
<b><span style='font-weight:bold'>Sent:</span></b> Tuesday, April 03, 2007 7:57
PM<br>
<b><span style='font-weight:bold'>To:</span></b> Roberta King<br>
<b><span style='font-weight:bold'>Cc:</span></b> Chimera BB<br>
<b><span style='font-weight:bold'>Subject:</span></b> Re: [Chimera-users]
viewing & comparison of multiple overlay structures</span></font><o:p></o:p></p>
</div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'>On Apr 3, 2007, at 1:47 PM, Roberta King wrote:<o:p></o:p></span></font></p>
</div>
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<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto'><font
size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>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.]</span></font><o:p></o:p></p>
</div>
</blockquote>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'></O:SMARTTAGTYPE></O:SMARTTAGTYPE></O:SMARTTAGTYPE>Hi Roberta,<o:p></o:p></span></font></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal style='margin-bottom:12.0pt'><span class=apple-tab-span><font
size=3 face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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.<o:p></o:p></p>
<div>
<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto'><font
size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>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.<o:p></o:p></span></font></p>
</div>
<p class=MsoNormal><span class=apple-tab-span><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceName"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceType"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place"><font
size=3 face="Times New Roman"><span style='font-size:12.0pt'>
</O:SMARTTAGTYPE></O:SMARTTAGTYPE></O:SMARTTAGTYPE></span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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"). <o:p></o:p></p>
</div>
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<blockquote style='margin-top:5.0pt;margin-bottom:5.0pt' type=cite><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceName"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceType"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place">
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<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto'><font
size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>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?<o:p></o:p></span></font></p>
</div>
</blockquote>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</O:SMARTTAGTYPE></O:SMARTTAGTYPE></O:SMARTTAGTYPE></span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>For more precise electrostatics, you can use an external
tool such as APBS or <st1:place w:st="on">Delphi</st1:place> 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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal style='margin-bottom:12.0pt'><span class=apple-tab-span><font
size=3 face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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).<o:p></o:p></p>
<div>
<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto'><font
size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceName"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceType"><O:SMARTTAGTYPE namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place">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)?</span></font><o:p></o:p></p>
</div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</O:SMARTTAGTYPE></O:SMARTTAGTYPE></O:SMARTTAGTYPE></span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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".<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><span class=apple-tab-span><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
</span></font></span>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.<o:p></o:p></p>
</div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
</div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'>--Eric<o:p></o:p></span></font></p>
</div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
<div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'>Eric Pettersen<o:p></o:p></span></font></p>
</div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'>UCSF Computer Graphics Lab<o:p></o:p></span></font></p>
</div>
<div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><a href="mailto:pett@cgl.ucsf.edu">pett@cgl.ucsf.edu</a><o:p></o:p></span></font></p>
</div>
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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><a href="http://www.cgl.ucsf.edu">http://www.cgl.ucsf.edu</a><o:p></o:p></span></font></p>
</div>
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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
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