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

From: Nassar, Omneya (omnassar_at_UTMB.EDU)
Date: Sat Jul 21 2018 - 07:58:40 CDT

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, Jrme Hnin <jerome.henin_at_ibpc.fr<mailto: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<mailto: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.htmlb4526a72d31aea2546852%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.htmlbcc3f2c0496789c708d5eef97f81%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<mailto:omnassar_at_utmb.edu>
Phone: 409.772.0731

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