[Chimera-users] building a molecule in Chimera

Elaine Meng meng at cgl.ucsf.edu
Mon Jan 12 14:57:26 PST 2015

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.

(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:


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. 

I hope this helps,

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/editing.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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