Hi Somdev,
Your results look quite reasonable but you will need to simulate longer to get convergence. Why do you think you should have negative values? Debasing the results so that dG=0 in the water phase, a negative region would indicate methanol prefers the lipid bilayer environment over water.
If you look at the PMF curve in the tutorial, although it comes back down close to zero, at no point is the free energy negative, indicating methanol would prefer to remain in water using GAFF and lipid14 force fields. In the Orsi paper, it seems like the free energy for methanol is very slightly negative around the lipid head group region, however these simulations used a coarse grained membrane so it is hard to directly compare.
The logP for methanol is around logP = -0.5, so it prefers water over oil. logP doesn't always track directly with membrane partitioning but it is a good indicator. If you run the same PMF for something like benzene (logP ~ 2), it should certainly prefer the membrane environment with -ve free energy.
Best,
Callum
-----Original Message-----
From: somdev pahari <somdevpahari1.gmail.com>
Sent: Tuesday, September 29, 2020 4:25 AM
To: AMBER Mailing List <amber.ambermd.org>
Subject: [AMBER] PMF calculation
Dear Amber users,
I am trying to calculate PMF for the lipid membrane system and using this tutorial as a reference (
https://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_callumjd_AMBER-2DUmbrella-5FCOM-5Frestraint-5Ftutorial&d=DwIBaQ&c=ZbgFmJjg4pdtrnL2HUJUDw&r=HwsFjSfOtLupDR-NuCP430rdz1DD2LkJxNM3BsKSjrw&m=glKztQJkVaVEw8x6mt5z6eAYHOsRFnnr0EC8hgMFGK8&s=xtdgAIY30mJZ3ga2YeZkK2GDHVS9g672O7YCsr3B8xs&e= ) with Amber 18.
I am trying to reproduce some results as described in the tutorial as well as in this paper (
https://urldefense.proofpoint.com/v2/url?u=https-3A__doi.org_10.1021_jp903248s&d=DwIBaQ&c=ZbgFmJjg4pdtrnL2HUJUDw&r=HwsFjSfOtLupDR-NuCP430rdz1DD2LkJxNM3BsKSjrw&m=glKztQJkVaVEw8x6mt5z6eAYHOsRFnnr0EC8hgMFGK8&s=QLU7ZMNOXG81ve1WJAFSk8mN9-x4TIz5JiQYCmMPC14&e= ), also mentioned in the tutorial.
I did it for water and methanol. What I faced that in the case of methanol there do not have any single negative value as it should be. I took 0.5 A as window width and ran a test simulation of 5 ns for each. I know that it's not enough for convergence, still, am I missing something? Kindly help me out.
Thanks in advance.
Regards
Somdev Pahari
Research Scholar
NIT Rourkela
Odisha, India
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Received on Mon Sep 28 2020 - 14:00:02 PDT
