Re: alchemical FEP question

From: Chris Chipot (Christophe.Chipot_at_edam.uhp-nancy.fr)
Date: Sun Dec 21 2008 - 13:27:57 CST

Hi Sébastien,

now that a soft-core potential is available in the upcoming
2.7 version of NAMD to avoid end-point singularities, thanks
to Floris Buelens and Chris Harrison's efforts, implementation
of the single-topology paradigm would make little sense. Why?
Under most circumstances, electrostatic decoupling would be
necessary, zeroing off the charges and the Lennard-Jones
parameters separately, with a potential of mean force correction
to account for shrinking bonds. This translates to running two
independent simulations, when the dual-topology requires only
one. Yet, if you insist upon going for the single-topology route,
your script ought to do the following: (i) drive NAMD to generate
the trajectory representative of the reference state 0, (ii) alter
the PSF by updating the charges according to q(λ) = λ q1 + (1-λ) q0
(first leg of the alchemical transformation), (iii) alter the
parameter file by scaling the Lennard-Jones parameters according
to Rij*(λ) = λ Rij*1 + (1-λ) Rij*0 and εij(λ) = λ εij1 + (1-λ) εij0
(second leg of the alchemical transformation), (iv) loop over the
configurations representative of state 0 and evaluate the potential
energy for state 1, (v) determine the ensemble average
<exp [-β(U1-U0)]>0. In principle, a PMF-bond correction (see
Pearlman and Kollman, as well as Hermans, back in 1991 for further
detail) ought to be measured as well. I may still have a script that
does the trick, but I would have to dig it out from archives.

Chris

seleg25_at_rsvs.ulaval.ca a écrit :
> Hi Christophe and Namd users,
>
> I am interested in that script that would make Namd pretend it do single
> topology (without fixing atoms). I am working on one but if there is already one
> somewhere I would like to see it.
> Are there any plans of implementing single topology in Namd?
>
> Thank you
>
>
> Sébastien Légaré
> Ph. D. Student
> Laval University, Quebec
>
>
> Selon Christophe.Chipot_at_edam.uhp-nancy.fr:
>
>> Hi Nandhini,
>>
>> what you are proposing to do is a single-topology transformation, wherein
>> only
>> the electrostatic component of your potential energy function is altered.
>>
>> In Namd, the paradigm chosen for alchemical transformations is
>> dual-topology,
>> where the topologies of both the reference and the target states coexist.
>>
>> Though you could cook up a quick-and-dirty script that would do the trick
>> and
>> pretend that Namd handles a single topology, I would advocate that you stick
>> to the dual-topology paradigm, branching out your molecule into two
>> topologies
>> where the charge distribution starts to differ (consider the charge
>> distribution
>> of the initial and the final states).
>>
>> Chris
>>
>>
>>
>> Selon Nandhini Sokkalingam <at5629_at_wayne.edu>:
>>
>>> Hello all,
>>> I am trying to mutate an aromatic compound to another one. The charges on
>> the
>>> atomic sites for the initial and the target molecule are different while
>> some
>>> of the
>>> sites have similar vdw parameters. can i fix the positions of the
>> specific
>>> atoms with
>>> similar vdw parameters to account for only electrostatic perturbation and
>> not
>>> for
>>> the non-bonded perturbation like in the charging of the sodium atom
>>> alchemical
>>> FEP tutorial.
>>>
>>> Thanks
>>> Nandhini
>>>
>>>
>>
>>
>
>
>
>

-- 
_______________________________________________________________________
Chris Chipot, Ph.D.
Equipe de dynamique des assemblages membranaires
Unité mixte de recherche CNRS/UHP No 7565
Université Henri Poincaré - Nancy 1           Phone: (33) 3-83-68-40-97
B.P. 239                                      Fax:   (33) 3-83-68-43-87
54506 Vandoeuvre-lès-Nancy Cedex
                             E-mail: Christophe.Chipot_at_edam.uhp-nancy.fr
                                            http://www.edam.uhp-nancy.fr
              The wretch, concentred all in self,
              Living, shall forfeit fair renown,
              And, doubly dying, shall go down
              To the vile dust, from whence he sprung,
              Unwept, unhonored, and unsung.            Sir Walter Scott
_______________________________________________________________________

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