[gmx-users] Size of perturbed groups in FEP

David Mobley dmobley at gmail.com
Wed Jan 11 16:47:17 CET 2006


I'm not an expert on free energy calculations involving mutation of
one thing into another; most of the calculations I do involve
disappearing of things. In that case (that is, the case of, say,
disappearing an isoleucine sidechain) you can certainly do it. It will
probably, however, be a lot harder to disappear the side chain in one
form and then appear it in another; it's hard enough to get converged
answers for the former, IMO. I think I might think about mutating both
to a common reference state so that you can get the free energy
difference by doing two disappearing calculations. Obviously this
takes "longer" than doing one calculation to bridge the whole gap, but
on the other hand it may be easier to get good convergence.

Others who have experience with this may be better prepared to comment.

One other thing: For these calculations, careful error analysis is
very important (in order to be sure you're not just seeing noise). You
need to take into account the time correlation in the data series; the
standard error isn't simply the square root of the variance divided by
the number of samples -- you need to correct for the fact that the
samples are correlated. This can make a big difference as the
correlation time is often fairly long compared to 1 or 2 fs.

Best wishes,
David Mobley
Postdoc, Dill lab, UCSF

On 1/11/06, Bruce Milne <bfmilne at ff.up.pt> wrote:
> Hi everyone,
> I have been wondering about the possibility of doing free energy
> calculations on D- and L- forms of amino acids incorporated into small
> peptides but I have no experience in this area and I was just wondering
> if it is possible to do free energy perturbations on groups as large as
> the side chains in e.g. isoleucine. It seems to me that changing a
> hydrogen atom for, say, a methyl group might be OK but what about
> something as large as -CH(CH3)CH2CH3 ?
> I guess in practice the unit to be perturbed would have to include the
> backbone carbon plus the hydrogen and side chain in order to go from the
> D- to the L-form of an amino acid.
> Sorry if this is really basic and obvious but any advice would be
> greatly appreciated.
> Cheers,
> Bruce
> --
> Dr. Bruce F. Milne PhD
> Faculdade de Farmácia
> Universidade do Porto
> Rua Aníbal Cunha - 164
> 4050-047
> Porto
> Portugal
> email: bfmilne at ff.up.pt
> CEQOFFUP: http://www.ff.up.pt/ceqoffup/ceqoffup.html
> Faculdade de Farmácia: http://sigarra.up.pt/ffup/web_page.inicial
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