[Chimera-users] Ligand Binding to Homodimeric Proteins
nancy5villa at gmail.com
Sun Jan 17 19:59:42 PST 2010
Thank you very much for your detailed reply.
On Sun, Jan 17, 2010 at 8:49 PM, Elaine Meng <meng at cgl.ucsf.edu> wrote:
> Hi Nancy,
> This is a general modeling question, not a Chimera question (since Chimera
> doesn't do automated docking) and would be better sent to a general forum
> such as ccl.net
> However, I'll attempt a brief and necessarily general answer.
> (a) It could be that the two binding sites are slightly different. This
> would not necessarily represent errors in the coordinates; perhaps the
> crystallization environment introduces slight asymmetries, or perhaps the
> two binding sites have some positive or negative cooperativity.
> (b) Even if the binding sites are "really" symmetrical, very small
> differences in coordinates, well within experimental uncertainty even at
> high resolutions, could cause large differences in the results. Say one
> atom is shifted by 0.001 A -- that could cross some cutoff in the method and
> prevent the ligand from fitting into one copy of the site.
> (c) Even if the coordinates for the two binding sites are exactly the same,
> there may be asymmetries introduced by how the docking program describes the
> sites or how it docks ligands into the sites. For specifics, you would have
> to look at the documentation for that program, or contact its support
> address, if any.
> I hope this helps,
> 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 17, 2010, at 5:14 PM, Nancy wrote:
> Hi All,
>> I am performing molecular docking simulations of a ligand binding to a
>> homodimeric protein, to determine a potential binding site(s). Due to the
>> symmetrical nature of a homodimer, I would expect that the binding site(s)
>> on one protomer would be identical on the other protomer. Therefore, a
>> ligand should bind with equal probability and affinity to both sides of the
>> protein. However, when I perform a molecular docking simulation (using an
>> X-Ray crystal structure), the ligand preferentially binds to one side of the
>> Is this outcome likely the result of errors inherent in the X-Ray crystal
>> structure, as one would expect identical binding to both sides?
>> Thank you very much.
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