Re: strange result using implicit solvent

From: Aron Broom (
Date: Fri Mar 29 2013 - 12:04:43 CDT

In addition to the comments already about ensuring you have the right bound
configuration, and that maybe implicit solvent and/or your forcefield may
just not work, did you have SASA on in your config file? I think by
default it is off, and turning it on will attempt to more fully capture the
hydrophobic effect (I think that without it you are essentially working
with 80-90% of the effect due having CDW interactions between protein and
ligand, but none for water).


On Fri, Mar 29, 2013 at 10:41 AM, Branko <> wrote:

> Fugui,
> If you use ligand docked to active site, it is high probability that
> ligand leave active site, so retry with the same settings and
> co-crystalized ligand on the same or on the similar protein. Using of
> explicit solvent is always better choice. Try to find force field with
> which you can treat BOTH protein and ligand (variance of CHARMM exist), and
> use the same type of charges for the protein and for the ligand (Gastieiger
> for example).
> Branko
> On 3/29/2013 2:39 PM, Niklaus Johner wrote:
> This isn't strange, it just means your ligand is not stable in the
> binding-site. The most likely problems in my opinion are either your
> force-field, your docking pose or your equilibration procedure.
> What force-field are you using? From what I know using gaussian for
> parameterization gives partial charges that aren't necessarily compatible
> with the CHARMM force-field. Maybe run a simulation of just the solvated
> ligand, to make sure your dihedral terms are ok and that it samples the
> conformations you expect.
> If you are confident in your binding pose, parameters and equilibration
> procedure, then maybe the implicit solvent representation isn't good enough
> for that particular case, so try to run an explicit solvent simulation.
> N
> Niklaus Johner
> Weill Cornell Medical College
> Harel Weinstein Lab
> Department of Physiology and Biophysics
> 1300 York Avenue, Room D-501
> New York, NY 10065
> On Mar 29, 2013, at 9:00 AM, Fugui wrote:
> Dear all,
> I used implicit solvent to do a MD of a protein-ligand complex, however,
> i got a very strange result. The ligand came out of the binding pocket. I
> used gaussian03 to produce the force filed of the ligand, i have no idear
> about the reason , could anyone give me some advices?
> By the way, i got strange results using 999 and 16 for cutoff.
> BW
> Fugui

Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo

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