[gmx-users] ligand falling out of active site during EM

David Mobley dmobley at gmail.com
Mon May 8 18:22:45 CEST 2006


On 5/8/06, Diane Fournier <diane.fournier at crchul.ulaval.ca> wrote:
> Still on the same problem, I made a pr run on the complex, and had the same result (ligand is out of the active site at time = 0.000 ps. Then I ran the same pr run, but with dt = 0.001 ps with all coordinates output for my trajectory. It turns out the ligand starts out of the active site, even if my input coordinates have the ligand inside. What is happening ??

First, if you are doing energy minimization, dt does nothing...

But second, double-check where it starts. For example, generate a tpr
file and then use trjconv to convert your initial gro file to a pdb
file and open it up with some viewer (i.e. pymol) (Or I guess use vmd
to visualize your starting gro file). See if the ligand starts outside
the binding site.

If so, then it probably means you've done something in a funny order.
For example, if you use editconf and genbox on just the protein before
adding the ligand, well, those tools re-center teh protein in the box,
so it will get shifted relative to the ligand (and hence the ligand
will no longer be in the binding site). I think the solution to that
is to use editconf or genbox on the system (protein+ligand), not just
the protein. If that isn't the problem, it might be worth e-mailing
the list exactly the steps you're following, and double-checking that
the initial protein and ligand coordinates prior to setting up the
system in GROMACS have the ligand in the binding site.


> -----Original Message-----
> From: gmx-users-bounces at gromacs.org on behalf of Diane Fournier
> Sent: Fri 5/5/2006 3:05 PM
> To: gmx-users at gromacs.org
> Subject: [gmx-users] ligand falling out of active site during EM
> Hello !
> I'm trying to run a molecular dynamics on a drug-enzyme complex. I did John Kerrigan's tutorial and everything worked fine. Now I'm trying with my system but I get a problem : the ligand keeps falling out of the active site during EM. I thought maybe it was a pbc problem and used comm-grps = protein in my .mdp file, but I get the same result. I transformed the .gro input file to .pdb to view it in pymol and the ligand is in the active site before simulation. So it seems this happens during steepest descents EM.
> The ligand is a hybrid inhibitor containing a steroid moiety (estradiol) linked to an adenosine-like moiety with a 13-methylene alkyl chain.
> Is there a way to keep/force the ligand in the active site during EM (maybe using PR) ?
> Is this reflecting some physical phenomenon, ie the ligand has low affinity ?
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