[gmx-users] Free energy in octanol and water
gmxquestions at gmail.com
Wed Sep 30 09:13:31 CEST 2015
Thanks, that is a good suggestion, I will try that.
Besides running multiple replicates, is there something else that is
obviously wrong with my method?
2015-09-29 19:09 GMT+02:00 Justin Lemkul <jalemkul at vt.edu>:
> On 9/29/15 4:51 AM, Gmx QA wrote:
>> Hi gmx-users
>> I am trying to calculate the free energy of solvation for a drug-molecule
>> in octanol and water.
>> I am comparing two situations:
>> A: Two systems, one with the drug in water only, and one with the drug in
>> pure octanol.
>> B: drug in water only (same as in A), and then one box where I have added
>> 20% water to my octanol system (since mixtures of octanol and water
>> typically contains some water in the octanol phase).
>> Then I run a series of free energy calculations per Justin's tutorial, 48
>> lambda points in total.
>> For system A I get a Delta-G for pure water of 39.07 kJ/mol, and 92.81
>> kJ/mol in pure octanol.
>> For system B, the Delta-G for pure water is the same, but for the
>> octanol-box with 20% water the Delta-G is 95.99 kJ/mol.
>> All of these results are obtained using gmx bar in gromacs 5.0.4.
>> My main concern is that the Delta-G is higher in the water/octanol mixture
>> than in pure octanol, but I would have expected the reverse to be the
> From experience, I can tell you it is very hard to get good convergence on
> such mixtures. You'll note that in npt.gro you effectively have two bands
> of water formed in the box, neither or which is particularly close to the
> API molecule. You'll probably get some microscopic phase separation. The
> route I've gone in the past is to generate several starting configurations
> (different random seeds when inserting the water molecules) and averaging
> over multiple runs. You should also do some error analysis of your results
> (both block averaging for convergence, and to compare the two DG values
> between the systems). Without error bars, you have no idea if those two
> values are at all meaningfully different.
> Is there something wrong with my protocol? The forcefield is
>> GAFF/amber99sb,and all production runs are 10 ns in length.
>> I have uploaded copies of all input-files here:
> 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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