[gmx-users] FEP vs PMF

Thu Nov 24 00:04:48 CET 2016

On 11/23/16 11:29 AM, Alex wrote:
> Thanks Billy,
>
> If so, then, what do you call the what you get from only one leg of the
> thermodynamic cycle? I mean calculation of only for example bound(complex)
> state or unbound(ligand) state.
>

Any leg of a thermodynamic cycle is DG.  The summation of these terms gives you 
the DG value for the process of interest.  This is an absolute free energy, e.g. 
binding free energy, hydration free energy, etc.  You only get DDG if you are 
taking the difference between DG values in a relative free energy calculation.

> How the DDG should be calculated?
>

A binding process is not a relative calculation.  It's an absolute binding free 
energy.  You're not going to get DDG for anything here unless you're comparing 
DG(molecule1) - DG(molecule2) in different binding processes.

-Justin

> To which experiment quantity those PMF and FEP are comparable?
>
> Thanks,
> Cheers,
> Alex
>
> On Wed, Nov 23, 2016 at 3:52 PM, Billy Williams-Noonan <
> billy.williams-noonan at monash.edu> wrote:
>
>> 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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>>>>>>>>>>
>>>>>>>>>> --
>>>>>>>>>> Billy Noonan*    |    *PhD Student    *|*    Bsci ( *Adv* ), IA
>> Hon
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>>>>>>>> --
>>>>>>>> Billy Noonan*    |    *PhD Student    *|*    Bsci ( *Adv* ), IA Hon
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>>>>>> --
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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
>>>> http://mackerell.umaryland.edu/~jalemkul
>>>>
>>>> ==================================================
>>>>
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>>
>>
>>
>> --
>> Billy Noonan*    |    *PhD Student    *|*    Bsci ( *Adv* ), IA Hon
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>> Royal Parade, Parkville, 3052
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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
http://mackerell.umaryland.edu/~jalemkul

==================================================