Re: Dual Topology in FEP Calculations - How to Calculate Electrostatics and van der Waals Free Energies Separately?

From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Mon Jul 23 2018 - 16:12:28 CDT

All particles are present at all times; their interactions vary. I think
there was more to your question, but I didn't get it.

Jerome

On Sat, 21 Jul 2018 at 14:59, Nassar, Omneya <omnassar_at_utmb.edu> wrote:

> Thank you Jerome for your prompt response. If you could further answer
> this question, I will greatly appreciate it. So at FEP lambda 0.0625 to
> 0.125, if I have 0,0 for alchVdwLambdaEnd, alchElecLambdaStart,
> respectively, do I have the geometry of NADH and ADP present or do I have
> the geometry of the intermediate at 0.0625 to 0.125?
>
> Thanks!
>
> Omneya
>
> On Jul 21, 2018, at 6:02 AM, Jérôme Hénin <jerome.henin_at_ibpc.fr> wrote:
>
> Dear Omneya,
>
> Your simulation parameters seem correct to me, as does your understanding
> of the alchemical process in this implementation.
>
> Best,
> Jerome
>
> On Fri, 20 Jul 2018 at 22:07, Nassar, Omneya <omnassar_at_utmb.edu> wrote:
>
>> Hello NAMD staff,
>>
>> I am trying to properly implement the dual topology paradigm in Free
>> Energy Perturbation technique for a mutation of NADH to ADP. I want to
>> calculate two things: 1) the van der Waals free energy of NADH changing to
>> ADP and 2) the electrostatics of NADH changing to ADP. Thus, I should have
>> values for dGvdw and dGelec from two separate simulations. However, after
>> reading over the documentation (
>> http://www.ks.uiuc.edu/Research/namd/2.7/ug/node53.html
>> <https://na01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.ks.uiuc.edu%2FResearch%2Fnamd%2F2.7%2Fug%2Fnode53.html&data=02%7C01%7Comnassar%40UTMB.EDU%7C099dbcc3f2c0496789c708d5eef97f81%7C7bef256d85db4526a72d31aea2546852%7C0%7C1%7C636677677711073805&sdata=ahfoJSCH4i7e6sVP6dY4rWsBU5WB372Idz9USilrGXE%3D&reserved=0>),
>> it seems that it is not possible to properly separate van der Waals and
>> electrostatics calculations using FEP.
>>
>> However, in contrast to my understanding of the above documuntation and
>> according to this very general response (
>> http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l.2010-2011/1722.html
>> <https://na01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.ks.uiuc.edu%2FResearch%2Fnamd%2Fmailing_list%2Fnamd-l.2010-2011%2F1722.html&data=02%7C01%7Comnassar%40UTMB.EDU%7C099dbcc3f2c0496789c708d5eef97f81%7C7bef256d85db4526a72d31aea2546852%7C0%7C1%7C636677677711073805&sdata=WOaQxK6X%2B038lGSGPbfUnswBbf0vH7%2Bwp%2Ffqfr42%2B74%3D&reserved=0>),
>> it is claimed that it is possible to separate vanderwaals and
>> electrostatics.
>>
>> Below is the input for van der Waals and electrostatics for each lambda
>> value (I am simulating each lambda window independently).
>>
>> ____________________________________________________________
>> VANDERWAALS CALCULATION/SIMULATION:
>>
>> # FEP PARAMETERS
>>
>> source fep.tcl
>>
>> alch on
>> alchType FEP
>> alchFile N3A_ion.fep
>> alchCol B
>> alchOutFile $outname.fepout
>> alchOutFreq 500
>>
>> alchVdwLambdaEnd 1.0
>> alchElecLambdaStart 1.0
>> alchVdWShiftCoeff 5.0
>> alchDecouple on
>> alchEquilSteps 1000
>> set numSteps 6251000
>>
>>
>> runFEP 0.6875 0.71875 0.03125 $numSteps
>> ______________________________________________________________
>> ELECTROSTATICS CALCULATION/SIMULATION:
>>
>> # FEP PARAMETERS
>>
>> source fep.tcl
>>
>> alch on
>> alchType FEP
>> alchFile N3A_ion.fep
>> alchCol B
>> alchOutFile $outname.fepout
>> alchOutFreq 500
>>
>> alchVdwLambdaEnd 0.0
>> alchElecLambdaStart 0.0
>> alchVdWShiftCoeff 5.0
>> alchDecouple on
>> alchEquilSteps 1000
>> set numSteps 6251000
>>
>>
>> runFEP 0.6875 0.71875 0.03125 $numSteps
>>
>> Using the input examples above, am I properly separating electrostatics
>> and van der waals calculations? If so, how is the geometry of the molecule
>> affected when I run the electrostatics calculation? Do I have both NADH and
>> ADP present geometrically, but only the charges are changing?
>>
>> Your help is invaluable and I really appreciate your response.
>>
>> Thank you!
>>
>> Omneya Nassar
>> PhD Candidate in Pharmacology and Toxicology
>> University of Texas Medical Branch
>> 301 University Blvd
>> Galveston, TX 77555
>> E-mail: omnassar_at_utmb.edu
>> Phone: 409.772.0731
>>
>>

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