Re: AMBER: equilibration in explicit solvent

From: Carlos Simmerling <>
Date: Mon, 05 Feb 2007 13:35:30 -0500

We recently published a detailed analysis of solvation free energies
for peptide conformations in various GB models compared to
explicit water. The article is available in the ASAP section of the
J Phys Chem B web site. Our approach (used by others as well) might be
a better way to see what the effect of GB is on your relative
free energies. Based on our experience, I would expect the use of GB vs.
explicit water to have a large effect on your results, so I am glad to see
that you are using explicit solvent to validate your GB results.
However, it's not very easy to get a quick free energy answer with
explicit solvent, as others have already brought up in this thread.
Without knowing which GB models you used, it is hard to say much more.

Roe, D., Okur, A., Wickstrom, L., Hornak, V. and Simmerling, C.,
/“Secondary Structure Bias in Generalized Born Solvent Models:
Comparison of Conformational Ensembles and Free Energy of Solvent
Polarization from Explicit and Implicit Solvation”/, J. Phys. Chem. B,
in press

Amarda Shehu wrote:
> I see. So it will involve playing around with the dimensions to ensure
> the same number of water molecules.
> These two conformations have been obtained with a newly developed
> method in implicit solvent (using ff03 and GB). I am preparing a
> manuscript for publication, but my advisor has asked me to make sure
> that in explicit solvent, these conformations retain both their
> structural integrity and their energetic difference.
> With the NVT equilibration (same dimension for boxes -- about 214
> water molecules difference), I have been able to see that the
> structures at the end of the equilibration remain very similar (0.5 A
> all-atom least RMSD) to the structures at the beginning of the
> equilibration. I made sure the equilibrations were rather long.
> The problem is that the final energies between the two structures are
> in the order of thousand of kcal/mol. The initial conformations, in
> implicit solvent, differ from each-other in less than 0.5 kcal/mol.
> After the equilibration, the difference is rather large. Most of this
> may be attributed to the difference of 214 water molecules.
> I am not sure whether simply counting out the water contribution
> (which I do not know how to do either) and reporting the energy
> difference between the two conformations without the water molecules
> is enough. I was told to seek an equilibration that from the start
> would have the same number of water molecules and the same density at
> the end.
> -Amarda
> On Sun, 4 Feb 2007, David A. Case wrote:
>> On Sun, Feb 04, 2007, Amarda Shehu wrote:
>>> I am trying to equilibrate in explicit water two conformations of
>>> the same
>>> system, separately. I followed some amber tutorials on how to add a
>>> water
>>> box and how to carry out an NVT equilibration. The problem is that a
>>> box
>>> of the same dimensions produces a different number of water
>>> molecules in
>>> each case. The difference is around 200 water molecules.
>>> Since I want to compare the final energies of the conformations
>>> after the
>>> equilibration,
>> This is likely to be a disappointing exercise, since fluctuations in the
>> (potential) energy will be large, and differences in the averages are
>> difficult
>> to interpret in any event. What is it that you really want to estimate?
>>> I want to maintain the same number of water molecules in
>>> each box. Is there a way to do this from the start? I have tried
>>> playing
>>> with different box dimensions for each of the systems but this is a
>>> very
>>> difficult hit-and-miss. I cannot find anywhere in the manual a way
>>> to do
>>> this.
>> Hit and miss might be the easiest strategy. Once you get close, just
>> create a
>> pdf file of the one with the slightly larger number of waters, and
>> manually
>> delete a few. Then re-load the resulting pdb back into LEaP.
>>> In addition, I want to run an NPT equilibration after the NVT one.
>>> Can one
>>> point me to a tutorial on how to do so? I have to make sure that the
>>> densities at the end of the simulations are the same
>> You can't do this: with different solvents, the equilibrium densities
>> will be
>> probably not be exactly the same. See my first comment above.
>> ...regards...dac
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Received on Wed Feb 07 2007 - 06:07:22 PST
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