From: Michael Grabe (Michael.Grabe_at_ucsf.edu)
Date: Tue Feb 28 2006 - 12:09:50 CST
Don't you worry that fixing the ions might give you the wrong
free energy value? In the simplest case, what if the dynamics
of the ion were important for its interaction with the solvent?
I have done a series of FEP calculations with Na to K in water
and I get very different shapes for free energy versus lambda
if i restrain the ions to a fixed position space with different size
spring constants. most notably the spread in the calculated
energies is very small with a strong spring, but it is more varied
with a weak spring.
I would appreciate comments on this from people.
On Feb 28, 2006, at 8:00 AM, jsachs_at_mail.csb.yale.edu wrote:
> That's what I did in my BJ publication on ion/mmebrane interactions
> (Sachs et
> al, Biophysical J. 2004), though I did it with CHARMM and in water, it
> fine...so that's also what I recommend...Jonathan
> Quoting Jérôme Hénin <jerome.henin_at_uhp-nancy.fr>:
>> In your case, the dual-topology approach may not be the best-suited,
>> the partly environment-decoupled ions are free to wander about the
>> box and clash with the solvent.
>> What you could do is emulate a "single-topology" perturbation by
>> keeping both
>> your ions fixed (NAMD fixedAtoms), in the very same position.
>> although I can see no reason why it should fail, I have never tried
>> that sort
>> of trick).
>> Please let us know how it works.
>> Le Samedi 25 Février 2006 07:40, Jawahar Neelankatan a écrit :
>>> I had a few questions about alchemical free energy perturbation
>>> simulations. I am getting strange and inconsistent results for an
>>> alchemical free energy perturbation simulation that I'm doing. I am
>>> transforming a K+ ion to an Na+ ion in a box of ~200 methanol
>>> (solvent). So basically the only atoms involved in the
>>> transformation in
>>> the FEP simulation are K (initial state, vanishing) and Na (final
>>> appearing) and thus they are prevented from interacting with each
>>> other by
>>> a modification (exclusion list) I made in the !NNB (non-bonding)
>>> section of
>>> the psf file, using the alchemify program. The K and Na ions are
>>> allowed to interact with the bulk solvent (methanol) molecules. I
>>> also have
>>> a .fep file defined that contains the ~200 methanol molecules, K ion
>>> and Na
>>> ion. I wasn't sure whether to give both K and Na ions the exact same
>>> coordinates or not. I didn't think it'd make a difference since they
>>> interacting to begin with. I went ahead and gave both of them the
>>> same coordinates in the .fep file. I then ran a 10000 step (2 fs per
>>> simulation with 5000 steps for equilibration and 5000 steps for
>>> sampling. I
>>> made delta_lambda = 0.025 to allow 40 windows for the growth of
>>> lambda from
>>> 0 to 1. The results I get don't bear much similarity to experimental
>>> results and in the .fepout output file, I'm seeing a few
>>> large values (999999999) for the vdW(l+dl) i.e. the van der Waals
>>> for the lambda2 state in each window. Is this normal ? I modified
>>> the .fep
>>> file so that K and Na don't have the same coordinates (as they did
>>> in the
>>> first simulation) but then I get the 'constraint failure in RATTLE
>>> algorithm' error. However, I inserted a 'minimize 1000' command to
>>> the system before equilibrating and subsequently sampling and that
>>> doesn't occur anymore but I still get a few unrealistically large
>>> for vdW(l+dl) and erroneous values for dG.
>>> The configuration file and a small section of the .fep file are
>>> attached to
>>> this email. Does it matter that I'm using the OPLS force field ? Any
>>> suggestions are welcomed. Thanks.
>>> Yahoo! Mail
>>> Use Photomail to share photos without annoying attachments.
>> Jérôme Hénin
>> Equipe de Dynamique des Assemblages Membranaires
>> Université Henri Poincaré / CNRS
>> Tel : (33) 3 83 68 43 91 Fax : (33) 3 83 68 43 87
Michael Grabe, Ph.D.
Rock Hall RH482
1550 4th Street
San Francisco, CA 94143-0725
tel: ++ 415.476.0421
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