[gmx-users] Free energy of transfer with accuracy

[David Mobley]

Hi,

> Hi gmx-users,
> I have tried to calculate the free energy of transfer of
> a solute between two solvents by thermodynamic integration.
> However, the dgdl plot I have obtained is not smooth enough to ensure
> accuracy.
> I have used a non homogeneous spacing for lambda. The first is from 0.0 to
> 0.4 (dl=0.04),
> the second is from 0.405 to 0.48 (dl=0.005) and the third is from 0.48 to 1
> (dl=0.04).
> Overall, I was performed 40 simulations.
> As can be seen in the figure (
> http://cromo.ufabc.edu.br/~fileti/web/dgdl-transfer.jpg ),
> there is a large fluctuation in the region that goes from 0.40 to 0.48.
> Each simulation was carried out by 0.5ns preceded by 0.15ns of
> equilibration.
> I am using soft-core whose parameters are:
> ; Free energy control stuff
> free_energy              = yes
> init_lambda              = 0.00
> delta_lambda             = 0
> sc_alpha                 = 1.3
> sc-power                 = 1.0 (for this I also used 2).
> sc-sigma                 = 0.47
> In the example of the link sc-power=1, but I re-did the calculations with
> sc-power=1
> and I found the same behavior (although the format of the plot was a little
> different).

> Can you suggest me a way to calculate this free energy difference with
> accuracy?
> The perturbation free energy method could give better results?
> Thank you
> EEF

This does look alarming.

I would make a couple comments here:
1) Soft core parameters can be fairly sensitive. Michael Shirts and I
have both looked at these independently and we find that sc-power =
1.0 with an alpha of 0.5 is typically substantially better than most
other options. Even alpha = 0.47 or 0.53 can be much worse than alpha
= 0.5. Your dV/dlambda curve looks to me like your soft core values
are far from ideal and that you are seeing a huge peak near lambda = 0
for this reason.
2) Am I interpreting your e-mail correctly that lambda = 0 corresponds
to one solvent, and lambda = 1 corresponds to another? If so, I am
unclear on how exactly you're doing the transformation and could use
more detail on how you've set this up. A more straightforward (and
easier?) way to do this would be to transfer the solute to vacuum from
each solvent and then take the difference in the vacuum transfer free
energies. Please clarify which you're doing so we can help better.


David Mobley, Ph.D.
Assistant Professor of Chemistry
University of New Orleans
New Orleans, LA 70148
dlmobley at uno.edu
Office 504-280-6445
Fax 504-280-6860

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