[gmx-users] free energy: annihilation

[Mu Yuguang (Dr)]

Hi David,
Recently I repeated some free energy solvation calculations according to
the tutorial by David Mobly. I agree with him that when you do DMSO
which has some high partial charges, You should do calculations with
Coulomb and VdW separately. Otherwise unphysical results appear.

Best regards
Yuguang
 
Dr. Yuguang Mu
Assistant Professor
School of Biological Sciences
Nanyang Technological University
60 Nanyang Drive  Singapore 637551 Tel: +65-63162885 Fax: +65-67913856
http://genome.sbs.ntu.edu.sg/Staff/YGMu/index.php
 

-----Original Message-----
From: gmx-users-bounces at gromacs.org
[mailto:gmx-users-bounces at gromacs.org] On Behalf Of David Mobley
Sent: Saturday, August 26, 2006 9:05 PM
To: Discussion list for GROMACS users
Subject: Re: [gmx-users] free energy: annihilation

David,

> I'm trying to annihilate a complete DMSO box at constant volume. The
> dG/dlam values converge nicely but when I integrate the curve I get a
> Helmholtz energy that is almost exactly a factor of two different from
> the experimental value.

Maybe this is too basic, but are you doing the transformation in
vacuum also and subtracting? I assume you are trying to compute
something like a hydration free energy, which means you have to
complete a thermodynamic cycle that takes you from the full molecule
in water to the full molecule in vacuum. I don't know any way to do
this  in GROMACS currently without also doing a separate vacuum
calculation, because of the intramolecular interactions.

> Am I forgetting something here? Should I treat the intramolecular
> degrees of freedom in a special manner?

You can, but you don't have to. One thing that can sometimes help
convergence is to only turn off the intermolecular LJ interactions,
which you can do by modifying the pairs list and explicitly stating
appropriate LJ parameters, or (presumably) by using the new pairs
types that Berk implemented, although I still haven't tested these
myself.

>Currently I am only turning off
> the LJ and Coulomb terms. Should I turn off the angles and dihedrals
as
> well?

No, you don't want to do that.

The other thing that can make some difference is your protocol. In
particular:
(1) Are you turning off the LJ and Coulomb terms simultaneously? I've
always found that it is a lot harder to converge this calculation and
get reliable answers than if you do the Coulomb interactions first and
then do the LJ interactions.
(2) What soft core parameters are you using for the LJ interactions?
Some work much better than others.  (My free energy tutorial has some
information about doing the LJ transformation. If you want to do
something really basic, you could try reproducing my value for
methane:
http://www.dillgroup.ucsf.edu/group/wiki/index.php/Free_Energy:_Tutorial
.
I also list the soft core parameters that are "optimal" there.)
(3) Make sure your PME parameters are good enough; sometimes free
energy calculations can be pretty sensitive to this sort of thing
(4) How curved is your dV/dlambda plot? TI can end up making a
nontrivial amount of integration error, especially if you have nearly
equal positive and negative areas under the curve (in which case the
integration error could be on the same order of magnitude as the total
integral).

David


> David.
>
________________________________________________________________________
> David van der Spoel, PhD, Assoc. Prof., Molecular Biophysics group,
> Dept. of Cell and Molecular Biology, Uppsala University.
> Husargatan 3, Box 596,          75124 Uppsala, Sweden
> phone:  46 18 471 4205          fax: 46 18 511 755
> spoel at xray.bmc.uu.se    spoel at gromacs.org   http://folding.bmc.uu.se
>
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