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
part.
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.
-Justin
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
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
========================================
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