[gmx-users] Re: Ligand simulation for LIE with PME

[Justin Lemkul]

On 11/8/13 3:32 PM, Williams Ernesto Miranda Delgado wrote:
> Greetings again
> If I use a salt concentration for neutralizing the protein-ligand complex
> and run MD using PME, and the ligand is neutral, do I perform ligand MD
> simulation without adding any salt concentration? It could be relevant for
> LIE free energy calculation if I don't include salt in ligand (neutral)
> simulation, even when I simulate Protein-ligand system with salt?

My assumption would be that you should introduce as few differences as possible. 
  Consider what LIE is doing - it is attempting to estimate the free energy of 
binding from simple interaction energies.  If you determine the strength of the 
ligand-protein interaction in the presence of some higher ionic strength medium, 
and then determine only the strength of ligand-water interactions rather than 
the interaction of the ligand with the same medium, then I'd say the calculation 
is flawed.  Think of what is really happening in real life - the ligand has to 
partition out of the solvent and into the protein's binding site.  The solvent 
is uniform throughout that process.

-Justin

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Justin A. Lemkul, Ph.D.
Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441

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