[gmx-users] Re: positive Leonard Jones Energy (Mark Abraham)

Justin A. Lemkul jalemkul at vt.edu
Mon Sep 19 13:56:27 CEST 2011

Gideon Lapidoth wrote:
> Hi Mark,
> Thanks for your answer. My ultimate goal is to compare biding affinities 
> between different ligands to the same protein using the LIE method. two 
> things bother though; First is the relatively high electrostatic  energy 
> I got between the ligand and the solvent which is considerably higher 
> (about 5 times higher) than the electrostatic energy between the 
> molecule and the protein , therefore using the lie equation I got a 
> positive delta G of binding  which is obviously not correct (the LJ 
> energy values cannot compensate for the electrostatic energy 
> difference). Secondly, my more immediate concern is to understand why I 
> would get a positive LJ value.

What force field are you using?  How did you derive the ligand parameters 
(charge calculations, atom type assignment)?

I have seen the LIE equation give some very funny results in many cases, 
although I know others have used it successfully.  There are far more delicate 
methods for determining the values you seek (free energy calculations, umbrella 
sampling, etc), though these techniques require significantly more work on your 

If your goals are comparative, then the absolute values obtained should not 
matter much, right?  As long as you keep your systems internally self-consistent 
then you can still make comparative conclusions.  If your goals are 
quantitative, I'd suggest you need either better ligand parameterization (once 
you have a test system that reproduces some known value) and/or methodology.


> What do you think?
> Thanks,
> Gideon
>  > Hi all,
>  >
>  > I ran g_energy in order to calculate the LJ energy between a pip2
>  > (Phosphatidylinositol 4,5-bisphosphate) molecule and the
>  > solvent using GROMACS 4.0.7. the pip2  molecule is very polar and the
>  > avg. coulomb energy value I got between the ligand and solvent was ~
>  > 3100 KJ.
> An equilibrated condensed-phase system of mixed positive and negative
> charges using a normal biomolecular force field should have negative
> Coulomb PE.
>  > The solvent includes water molecules and Cl and Na ions to counter the
>  > pip2 charge. the production run was done in npt conditions. the total
>  > charge of the pip2 molecule is -6 e. The avg. LJ  energy I got was
>  > ~190 KJ.
>  > I am trying make sense of this. could it be that the polar
>  > interactions between the solvent and ligand are so strong that they
>  > can influence a positive LJ energy?
>  > Does anyone have any idea why this could be ?
> Force fields are parameterized to reproduce certain experimental or
> computational results, in the hope that such reproduction will permit
> simulations using that force field to sample similar chemical ensembles
> with correct frequencies. They're not parameterized such that the
> absolute values of any energies or energy components means anything, and
> one has to work hard to demonstrate anything sensible about energy
> differences, too. What were you hoping to observe?
> Mark
> -- 
> Gideon Lapidoth,
> MS.c candidate
> Hemi Gutman Biophysics Lab
> Department of Biochemistry & Molecular Biology
> George S. Wise Faculty of Life Sciences
> Tel Aviv University
> Israel 69978
> <http://ashtoret.tau.ac.il/>
> Tel: (972-3) 640-9824


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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