[gmx-users] problem with free energy calculations

Berk Hess gmx3 at hotmail.com
Tue Feb 6 09:08:47 CET 2007

>From: Michael Brunsteiner <mbx0009 at yahoo.com>
>Reply-To: Discussion list for GROMACS users <gmx-users at gromacs.org>
>To: gmx-users at gromacs.org
>Subject: [gmx-users] problem with free energy calculations
>Date: Mon, 5 Feb 2007 21:31:14 -0800 (PST)
>Dear all,
>I seem to have a problem with my free energy TI calculations
>using Gromacs, I'd be grateful for any suggestions about what
>could have gone wrong there...
>I calculated the free energy of solvation of water
>(basically its chemical potential). The literature value for TIP3P
>water, which I used, is about -6.3 kcal/mol -
>I get something like +2.5 (!) ...
>my calculations are fairly standard, I use PME with
>conservative parameters, soft core potentials,
>do 21 windows, each one lasting 500 pico seconds, then
>after discarding the first 100 ps of each dgdl*xvg file
>i use the averages and do a numerical integration,
>the works ...
>I also use two thermostates (one for the water that disappears,
>one for the rest)
>I see that the fluctuations of my dU/dlambda values are fairly
>large ... can it be that the soft core parameters i use (sc_alpha=0.7,
>sc_power=1, sc_sigma=0.3) are inappropriate if, as i do here,
>i turn on/off the VdW and Coulomb interactions simultanioulsy ??
>mdp plus topology files and the results are included below,
>thanks in advance for any suggestions!

One "obvious" problem is that using two thermostats is incorrect.
In this way the com of the water with respect to the com of the rest
will not be sampled correctly (both are fixed).
The solution is using the sd integrator.

Another issue is that since water is strongly hydrogen bonding
and the hydrogen bond interaction is rapidly soft-cored,
you probably need much closer spaced lambda point at lambda=0
(i.e. use an inhomogeneous spacing).

There could be other issues, but one would only find those
after studying the results in detail.


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