Re: FEP with flattened free energy surface?

From: Jérôme Hénin (jhenin_at_ifr88.cnrs-mrs.fr)
Date: Sat Apr 09 2011 - 01:18:19 CDT

On 8 April 2011 22:48, Ivan Vyalov <VyalovIvan_at_yandex.ru> wrote:
> Well, I took a protein as a common example, but the system is actually cellobiose in ionic liquid. That's why I have these differences and values of free energy don't change with time, so I think it's ok with respect to converrgence. But if I apply bias calculated at the point where the barriers are high, then in point where solute-solvent interactions are switched off my system will be over-biased, won't it?

Apparently, yes. One thing you could do is scale the restraints down,
possibly all the way to zero, as they become less relevant.

> 09.04.11, 00:05, "Jérôme Hénin" <jhenin_at_ifr88.cnrs-mrs.fr>:
>
>> 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
>>  >
>>  >
>>
>>
>>
>
> --
> with best regards,
> Ivan
>

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