[Chimera-users] building a molecule in Chimera

Mike mikej at nc.rr.com
Mon Jan 12 17:34:26 PST 2015


Hi Elaine,
Thank you so much for your reply!
You have described things perfectly.  I'll give it a try in the next few
days and hopefully things 
will go well.
Thank you!
Mike

-----Original Message-----
From: Elaine Meng [mailto:meng at cgl.ucsf.edu] 
Sent: Monday, January 12, 2015 5:57 PM
To: Mike
Cc: chimera-users at cgl.ucsf.edu BB
Subject: Re: [Chimera-users] building a molecule in Chimera

Hi Mike,
I got caught up in the building and forgot to address the subsequent steps
you'd mentioned.  So, to continue:

(A) energy-minimization can be done with Minimize Structure (in menu under
Tools. Structure Editing) or equivalently, the "minimize" command.
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/minimize/minimize
.html>

(B) people use "docking" to predict possible binding orientations of a small
molecule relative to a protein structure.  For high-level sampling of
orientations, including flexibility, or searching a whole database of small
molecules, you would have to use some other program outside of Chimera
(DOCK, AutoDock, GOLD, etc.) although there is a handy ViewDock tool for
looking at the results.  However, for just docking one small molecule to a
protein and only getting a small number of output orientations, you can use
the AutoDock Vina tool in the menu under Tools. Surface/Binding Analysis:

<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/vina/vina.html>

It runs AutoDock Vina using a web service and then shows the results in the
ViewDock tool.

You can also try to dock the structures by hand, e.g. freezing the protein
in place and moving only the small molecule, and even rotating bonds, but
this can be difficult.  I wouldn't recommend it unless you have some guiding
evidence such as residues known to contact the small molecule. 
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/mouse.html#activedef>
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/editing/editing.h
tml#adjust>

I hope this helps,
Elaine

On Jan 12, 2015, at 2:11 PM, Elaine Meng <meng at cgl.ucsf.edu> wrote:

> Hi Mike,
> There is no quick 2D sketching to create a small molecule, only 
> building it up atom-by-atom.  You can also enter a SMILES string or 
> specify a PubChem CID to generate a small molecule in Chimera, which 
> could be used as a starting point for further atom-by-atom building if 
> necessary.  It's easier than building the whole thing atom by atom. If 
> you don't want to deal with SMILES, you can search PubChem Compound to 
> find the CID number of your molecule or a similar molecule to use as a 
> starting point.  <http://www.ncbi.nlm.nih.gov/pccompound>
> 
> These options are all with the Build Structure tool (in menu under Tools.
Structure Editing).  See the Start Structure and Modify Structure sections
in that tool.
> <http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/editing/edi
> ting.html>
> 
> For example, after starting Build Structure in Chimera, in its Start 
> Structure section you could enter
> 
> SMILES string:  c1ccccc1OC
> or
> PubChem CID:  31231
> 
> . and click Apply to get the specified molecule.  Then you could
Ctrl-click one of the hydrogens to select it and change it to bromine using
the Modify Structure section of Build Stucture (Element: Br, Bonds: 1, click
Apply).  Or you could change it to a methyl group (Element: C, Bonds:4,
Geometry: tetrahedral, Apply) and then select one of the hydrogens on the
new methyl group to continue building out further.
> 
> I hope this helps,
> Elaine
> ----------
> Elaine C. Meng, Ph.D. 
> UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab Department 
> of Pharmaceutical Chemistry University of California, San Francisco
> 
> On Jan 10, 2015, at 2:01 PM, "Mike" <mikej at nc.rr.com> wrote:
> 
>> This is my first day with Chimera.  I'm trying to find how to draw a 
>> small molecule, minimize the structure of the small molecule and then
have it interact with my protein of interest.  However, I don't see any way
for me to draw a small molecule (potential drug).
>> Can you provide any direction ?
>> 
>> Thanks,
>> Mike





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