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

Justin Lemkul jalemkul at vt.edu
Fri Oct 12 15:43:59 CEST 2012

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 A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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