charging free energies with alchdecouple

From: Harris, Robert C. (rocharri_at_UTMB.EDU)
Date: Wed Dec 19 2012 - 11:29:08 CST

I am attempting to use the alchdecouple feature in NAMD to compute the van der Waal's and electrostatic components of the solvation energy of hexane separately with free-energy perturbation, but I think that I must have made some mistake in my input file. When I compute the van der Waal's component (by setting alchElecLambdaStart=1.0 and alchVdwLambdaEnd=1.0), everything seems fine, but the electrostatic component does not seem to be correct. The electrostatic component of this energy is computed to be about -2 kcal/mol, while I was expecting values smaller than -1.0 kcal/mol to be consistent with results in the literature. The lines where I set up the FEP are as follows:

alch on
alchType FEP
alchFile hexane_solv.fep
alchCol B
alchOutFile backward_electrostatics.fepout
alchOutFreq 1000
alchElecLambdaStart 0.00001
alchVdwLambdaEnd 0.0
alchDecouple on
alchEquilSteps 5000

set lambda 1.0

while {$lambda >= 0.04} {
      alchLambda $lambda
      set lambda [expr $lambda - 0.05]
      alchLambda2 $lambda
      run 100000

NAMD gives the change in electrostatic energy between lambda=1 and lambda=0.95 as -0.18 kcal/mol, but when I run a regular simulation at lambda=1, compute the electrostatic interaction energy between the hexane and water, and multiply by 0.05 I get -0.006 kcal/mol. Additionally, when I try to compute this energy with TI (by simply changing alchType to TI), the electrostatic component of du/dl was -0.11, which yields a dG of -0.11*0.05=-0.0055 kcal/mol, consistent with the second number. Another strange observation is that if I use alchElecLambdaStart=0.0, as was done in the FEP tutorial, the energy is given as infinite for all lambda windows. Did I make a mistake in my choices of alchElecLambdaStart and alchVdwLambdaEnd or in some other alchemical parameter? Thanks for any help you can give me.

Robert Harris

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