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: Sat Jul 21 2018 - 05:58:02 CDT

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), 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),
> 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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