[gmx-users] Position restraints and free energy calculations

Justin Lemkul jalemkul at vt.edu
Fri Feb 6 13:28:42 CET 2015

On 2/5/15 6:59 AM, Kortzak, Daniel wrote:
> Dear All,
> I want to calculate the free energy of binding of a single sodium ion to a protein. I want to do this by decoupling the ion in the binding site (with the couple-moltype approach). The work-flow I have in mind is roughly:
> 1. Start with ion in binding site
> 2. Turn on position restraints (since this only one atom I don't have to care about orientation etc.)
> 3. Decouple
> (And do the same for a ion in bulk solution in another simulation.)
> First of all is this sensible or are there better ways of doing this?

Wouldn't just using the pull code to do umbrella sampling be a much more 
straightforward approach?  You don't have to deal with compensating for 
artifacts associated with the restraint potential during decoupling and removing 
a charge from the system.


> Can I do 2. by normal position restraints in my topology or do I have to use a pull code? The former would be more easy to execute but the manual entry for the restraint-lambdas sounds like I have to do the latter.
> A more precise version of my question would be: Has the decoupling/annihilating procedure (in particular the value of the restraint-lambda) any effect on the position restraints defined in the [moleculetype] section of the decoupled molecule?
> Then another thing is, that it would be more convenient (convenient for me because I need less jobs in the queue I am not claiming that this would be more efficient) to do both decoupling of an ion in the protein and coupling another ion in solution in the same simulation. But as far as I understand the couple-moltype approach, I can only decouple an ion in protein and decouple another ion in solution which would give useless results if do this in the same simulation. The only solution to this I see, is to introduce dummy atoms and use the A-B-topology approach. Is this correct?
> Best regards and thanks in advance for reading,
> Daniel
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Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

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


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