Re: Overestimated PMF

From: JC Gumbart (
Date: Mon Jun 17 2013 - 11:37:10 CDT

Take a look at this paper and see if addresses your questions:

On Jun 17, 2013, at 10:43 AM, Felipe Merino wrote:

> Dear all,
> I know this is a little bit off topic but i think somebody could help us here. We have been doing some umbrella sampling simulations to calculate the binding free energy of a protein-DNA complex. We are using the minimal interatomic distance as reaction coordinate. The thing is that the protein has two domains and we are only pulling them separately, so in the end we have always an endpoint with the other domain still bound (that was planned). In the end, the binding free energies are much higher than expected (around 25 kcal/mol). The point is that it sounds to me that there should be a correction on the PMF to account for the "confinement" of being bound to the other (still attached) domain (very much line in the case where you restrain the ligand when doing FEP annihilation) but i am not sure if this is correct. Any insights for this will be highly appreciated.
> Best
> Felipe

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