[gmx-users] FEP vs PMF

Wed Nov 23 15:52:39 CET 2016

Hi Alex,

>From your PMF you get a DG of binding.  From an absolute FEP calculation
where you close the thermodynamic cycle, you _also_ get that same DG of
binding.  Just because you're subtracting or adding two values to close the
cycle doesn't make it a DDG value.

Yes you could compare both methods to experiment. :)

Cheers,

Billy

On 24 November 2016 at 01:34, Alex <alexanderwien2k at gmail.com> wrote:

> Thanks Justin.
>
> Ok, in PMF it is not DDG, but in FEP as far as I know it is DDG (binding
> free energy) when one complete the thermodynamic cycle as I have done here.
>
> Then, what is the DDG in a PMF?
>
> What could be comparable between "PMF and experiment" or between "FEP and
> experiment"?
>
> Thanks.
>
> regards,
> Alex
>
> On Tue, Nov 22, 2016 at 9:20 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
> >
> >
> > On 11/21/16 4:30 PM, Alex wrote:
> >
> >> what I have as PMF itself has been already harvested from gmx wham.
> >>
> >
> > This is not a DDG, it's just DG, the difference between the plateau
> > (unbound) and minimum (bound).  That's the value you compare with the FEP
> > result, though I'm not clear how one obtains a reasonable and converged
> > value for the FEP in bound and unbound states.  PMF is a very
> > straightforward method to do this.  FEP requires lots of other
> restraints,
> > etc that have to be accounted for.
> >
> > -Justin
> >
> >
> > Regards
> >>
> >> On Mon, Nov 21, 2016 at 10:24 PM, Billy Williams-Noonan <
> >> billy.williams-noonan at monash.edu> wrote:
> >>
> >> You could also do WHAM analysis with gmx wham. :)
> >>>
> >>> On 22 November 2016 at 07:48, Alex <alexanderwien2k at gmail.com> wrote:
> >>>
> >>> Yes, indeed the thermodynamic cycle is closed.
> >>>> If I am not wrong an integration like below should be done over PMF in
> >>>> order to get adsorption energy which is equivalent to \Delta\Delta G
> in
> >>>> FEP.
> >>>>
> >>>> \Delta F_{ads} = -K_{B}*T Log[ Integrate(exp(-PMF/K_{B}*T)/L)]
> >>>>
> >>>> in which L is the interval where PMF starts to its plateau.
> >>>>
> >>>> Regards,
> >>>>
> >>>> Alex
> >>>>
> >>>> On Mon, Nov 21, 2016 at 9:24 PM, Billy Williams-Noonan <
> >>>> billy.williams-noonan at monash.edu> wrote:
> >>>>
> >>>> Assuming you have closed the thermodynamic cycle correctly (which no
> >>>>>
> >>>> doubt
> >>>>
> >>>>> you have), then I would think you have just measured the same
> quantity
> >>>>>
> >>>> with
> >>>>
> >>>>> absolute FEP as you did using PMF with umbrella sampling.  You have
> the
> >>>>> same dG of binding, but with different methods. :-)
> >>>>>
> >>>>> Cheers,
> >>>>>
> >>>>> Billy
> >>>>>
> >>>>> On 22 November 2016 at 07:19, Alex <alexanderwien2k at gmail.com>
> wrote:
> >>>>>
> >>>>> Hi Billy,
> >>>>>>
> >>>>>> Thanks for your response,  whatever you want to call it, it is the
> >>>>>> difference between the free energies of the system in bonded(or
> >>>>>>
> >>>>> complex)
> >>>>
> >>>>> and unbounded(or ligand) states, so it is [\Delta G_{bounded} -
> >>>>>>
> >>>>> \Delta
> >>>
> >>>> G_{unbounded}].
> >>>>>>
> >>>>>> Regards,
> >>>>>> Alex
> >>>>>>
> >>>>>> On Mon, Nov 21, 2016 at 9:06 PM, Billy Williams-Noonan <
> >>>>>> billy.williams-noonan at monash.edu> wrote:
> >>>>>>
> >>>>>> If you're calculating an absolute free energy of dissociation, why
> >>>>>>>
> >>>>>> would
> >>>>>
> >>>>>> it
> >>>>>>
> >>>>>>> be a "\Delta\Delta G"?
> >>>>>>>
> >>>>>>> Kind Regards,
> >>>>>>>
> >>>>>>> Billy
> >>>>>>>
> >>>>>>> On 22 November 2016 at 04:12, Alex <alexanderwien2k at gmail.com>
> >>>>>>>
> >>>>>> wrote:
> >>>>
> >>>>>
> >>>>>>> Dear gromacs user,
> >>>>>>>>
> >>>>>>>> For a reaction (dissociation of a amino acid from a solid surface
> >>>>>>>>
> >>>>>>> in
> >>>>
> >>>>> aqueous solution), I have calculated the "\Delta\Delta G" by free
> >>>>>>>>
> >>>>>>> energy
> >>>>>>
> >>>>>>> perturbation method in alchemical analysis, and also for the same
> >>>>>>>>
> >>>>>>> reaction
> >>>>>>>
> >>>>>>>> I have calculated the PMF by umbrella sampling.
> >>>>>>>>
> >>>>>>>> I was wondering how I can compare these two results together?
> >>>>>>>>
> >>>>>>>> Thanks,
> >>>>>>>>
> >>>>>>>> Regards,
> >>>>>>>> Alex
> >>>>>>>> --
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> > --
> > ==================================================
> >
> > Justin A. Lemkul, Ph.D.
> > Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >
> > Department of Pharmaceutical Sciences
> > School of Pharmacy
> > Health Sciences Facility II, Room 629
> > University of Maryland, Baltimore
> > 20 Penn St.
> > Baltimore, MD 21201
> >
> > jalemkul at outerbanks.umaryland.edu | (410) 706-7441
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