Re: FEP, Ewald size-dependence charge correction

From: Sebastian Stolzenberg (ss629_at_cornell.edu)
Date: Sun Sep 07 2014 - 10:23:17 CDT

Dear All,

let me give you some free energy difference values (in kcal/mol) for the
email below:

FEP experiment 1 (L=67A):
75.96 (reverse run gives -75.50)
cr=-7.03

FEP experiment 2 (L=67A):
76.03 (reverse run gives -75.88)
cr=7.03

I also did the same FEP runs just for the annihilation of Na2 (i.e.
without an H2O appearing) and get the same odd result.

Can anybody tell me what I am conceptionally missing here?

Much appreciation,
Sebastian

Am 02.09.14 um 22:12 schrieb Sebastian Stolzenberg:
> Dear All,
>
> I stumbled over the following consistency check to see, whether I
> fully understand the size-dependent charge correction derived in
> Hummer, G.; Pratt, L. R.; Garcia, A. E. J. Phys. Chem. 1996, 100,
> 1206–1215,
> for FEP/TI with Ewald summation;
> this correction I denote here as cr=0.5*ξ*(q1^2-q0^2), where q0 and q1
> are the total charges of the simulated system in the reference and
> target state, respectively, ξ=−2.837/L, and L is the length of the
> cubic simulation box.
>
> Given:
> - cubic water box with length L=67A (or 128A) with 0.15mM NaCl,
> neutral net charge
> - standard CHARMM36 ff, NPT, PME, NAMD 2.9
>
> FEP experiment 1:
> annihilate an Na ion, and let appear a water molecule
> (the Na and OH2 atoms are harmonically restrained to the same {x y z}
> position)
> => q0=0, q1=-1
> => cr<0
>
> FEP experiment 2:
> prior to FEP, delete a CL ion in the box, then
> annihilate an Na ion, and let appear a water molecule
> (the Na and OH2 atoms are harmonically restrained to the same {x y z}
> position
> => q0=+1, q1=0
> => cr>0
>
> I understand that the corrected free energy difference DG_cr is
> obtained from the computed DG (e.g. via NAMD FEP) via:
> DG_cr=DG+cr
> I am confused because in my FEP simulations, DG is nearly identical
> for both FEP experiments stated above (to the second digit).
> Therefore, I would receive different values of DG_cr for the same
> alchemical transformation (Na to water).
>
> Is there something I missed along the lines?
>
> With Thanks and Best Regards,
> Sebastian
>

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