Re: FEP with flattened free energy surface?

From: Jérôme Hénin (jhenin_at_ifr88.cnrs-mrs.fr)
Date: Fri Apr 08 2011 - 15:05:30 CDT

Hi Ivan,

On 8 April 2011 21:12, Ivan Vyalov <VyalovIvan_at_yandex.ru> wrote:
> Hi Jerome,
>
> Thanks for reply! So, colvars config should contain lines like these:
>
> abf {
>  colvars phi psi
>  updateBias no
>  inputPrefix colvarA01o
>  fullSamples 200
> }

This looks fine. Setting the fullSamples parameter is a good idea, actually.

> And then I start FEP calculations that seems to be working ( I didn't try with solvent yet ).
>
>
> May I ask you one more question?
>
> If I want to perform annihilation of dipeptide then won't I have to recalculate bias ( along \phi & \psi ) between FEP steps ( perhaps, not between every lambda window )? In my case solvent changes free energy surface quite significantly and if I have barriers ~6 kcal/mol for vacuum then for solvent they are ~16 kcal/mol.

Well, you probably don't need the biases to be perfectly accurate,
they are just there to improve sampling. It is a bit surprising that
solvent effects on conformational free energy are so drastic. Are you
confident that the ABF calculations are converged (or close enough)?

In principle you can certainly apply different biases at different
stages, if you are ready to run more calculations. I am not sure it is
worth the effort. It depends on the specifics of your system (and how
much time you are willing to spend on it).

By the way, an idea just came to my mind: it might be a better idea to
replace the data in the gradient file with that in the '.est' file
written by abf_integrate. The good thing about that data is that it is
a "true gradient" (its curl is zero), whereas the raw data in the
'.grad' file is not, due to statistical noise. Applying the bias based
on the '.est' file ensures that the biasing force is conservative.

Best,
Jerome

> 06.04.11, 20:45, "Jérôme Hénin" <jhenin_at_ifr88.cnrs-mrs.fr>:
>
>> Hi Ivan,
>>
>>  That should be possible. Here is how I see it:
>>  1) run ABF to get biasing potential
>>  2) run FEP with ABF bias, disabling updatePotential to keep the bias
>>  time-independent.
>>  In this step, save FEP data and colvars trajectory with the same
>>  frequency (e.g. 10 timesteps) to make the next step easier
>>  3) compute a FEP estimator with unbiased data: you need to reweight
>>  the ensemble averages based on the applied ABF bias.
>>
>>  Cheers,
>>  Jerome
>>
>>  On 6 April 2011 11:49, Ivan Vyalov <VyalovIvan_at_yandex.ru> wrote:
>>  > Hi all,
>>  >
>>  > I wonder, is it possible to perform FEP calculations with solute molecule with flattened free energy surface along several reaction coordinates?
>>  >
>>  > For instance, if I take dipeptide with conformational degrees of freedom ( dihedrals \phi & \psi ) and two minima defined by them, I should take into account this minima and do something similiar to what is described in JPhysChem 97, 3409.
>>  >
>>  > From the other hand I could run ABF, apply forces and perform FEP with flat free energy surface along these coordinates, is it possible in NAMD? Or I should do such task in a different way?
>>  >
>>  >
>>  >
>>  > --
>>  > with best regards,
>>  > Ivan
>>  >
>>  >
>>
>>
>>
>
> --
> with best regards,
> Ivan
>
>

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