Re: Restarting protein system simulation using different ligand

From: Chris Harrison (
Date: Sun Oct 16 2011 - 18:41:55 CDT


You're likely experiencing high energy interactions between the binding
site atoms and your new ligand as the binding site has not had the
opportunity to sufficiently relax it's conformation such that the bound
complex is a favorable energetic state. The result of these high energy
interactions will be high forces which will become very high velocities
with which your atoms will "shoot" across your cell (maybe not the atoms
of your ligand but others such as those of the protein or water).
You've essentially instantly boiled your protein from the inside.

One solution may be to restrain the atoms of your protein and ligand and
then in a series of simulations, release in a step-wise fashion the
restraints. A simple example would be to initially release the
restraints on the ligand only and hope it remains within the binding
site and relaxes to accomodate it, then subsequently release the
restraints on the sidechain atoms, allowing them to relax around the
ligand while keeping the backbone atoms fixed to maintain overall
protein structure, and finally release all restraints.


Chris Harrison, Ph.D.
Theoretical and Computational Biophysics Group
NIH Resource for Macromolecular Modeling and Bioinformatics
Beckman Institute for Advanced Science and Technology
University of Illinois, 405 N. Mathews Ave., Urbana, IL 61801                          Voice: 773-570-0329              Fax:   217-244-6078
Kevin Kastner <> writes:
> Date: Thu, 13 Oct 2011 13:22:41 -0400
> From: Kevin Kastner <>
> To:
> Subject: namd-l: Restarting protein system simulation using different ligand
> I have been running an explicit solvent simulation in NAMD 2.8 containing a
> transmembrane protein, ligand, lipid membrane, water, and ions. I generated
> the system, excluding the ligand, using the NAMD membrane tutorial. I then
> add the ligand in and then convert it for use with the Amber force field. I
> run the three preparatory simulations, then however many full simulations I
> need.
> What I want to do is replace the ligand that is in the system at the end of
> the simulation with another one and continue the simulation. (I tried this
> before but it complained that I had exceeded the periodic cell boundary.) Is
> it possible to do this without having to remake the entire system from
> scratch? I doubt that I can use the .coor and .vel restart files as some
> atoms have been replaced, but would it be possible to use either the .xsc or
> .xst files, or is there a better way? Oh, and the ligand is contained within
> the protein, so (hopefully) it should not exceed the periodic cell boundary

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