[gmx-users] delta G of binding for protein-ligand complex

[Justin Lemkul]

On 10/12/12 5:44 AM, Archana Sonawani wrote:
> Dear Gromacs Users,
>
> I have two large organic compounds and one peptidomimetic binding to same
> receptor protein. I want to compare the delatG of binding of all the three
> complexes to show that peptidomimetic binds with greater affinity to
> protein. According to the gromacs tutorial,  I have to perform (de)coupling
> of the ligand in complex with the receptor and in bulk solution. I don't
> know exactly how to start with this process.
>

There is tons of literature on this topic.  The protocol is basically the same 
for performing decoupling in the receptor and in solvent; the only thing that 
differs is the environment.

> Do I need only the protein-ligand complex simulated for 5ns to start with?
>

Starting with an equilibrated structure of the protein-ligand complex is 
necessary, but it's not the only thing you need to do.  That's only half of the 
free energy calculation; the other half is done just in a box of water.  Again, 
refer to the literature and review articles on free energy methodology.

Another applicable technique is umbrella sampling, though it is likely to be 
more computationally expensive.

-Justin

-- 
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Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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