Hello Dr. Case,
Yes your right, we had discussed it a while back and so this time I reran my simulations (12 lambda 12 runs) with a restraint on my acetonitrile+ 5 protein residues surrounding it.
(ntr =1, restraintmask=’2,23,271,274’) 274 is my C3N and the others are protein residues...
So, even if the restraint is applied to not just the ligand but the ligand and the residues around it, even then how does it meander away to like 4-5 Angstroms from the initial site location?
Am I doing it wrong ?
May you kindly suggest me some ideas on how to make sure the ligand does not walk away from the protein or vice versa.
Thanks so much sir.
Debarati
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From: David A Case<mailto:david.case.rutgers.edu>
Sent: 04 October 2020 20:54
To: AMBER Mailing List<mailto:amber.ambermd.org>
Subject: Re: [AMBER] RMSD of ligand in pocket
On Sun, Oct 04, 2020, Debarati DasGupta wrote:
>
>While applying a restraint of 10kcal/mol on my C3N ligand, why does the
>rms fluctuations look like this...( Plot of 12 lambdas C3N RMSD over
>the production phase of TI runs)???
Is this perhaps the problem that was discussed a while ago? Are you
restraining the *ligand* to stay in its original location, but allowing
the protein to move? In that case, the restraint on the ligand
essentially has no effect at all: letting the protein move away from the
ligand is equivalent to letting the ligand move away from the protein.
If you then run your cpptraj script, which superimposes the protein
frames onto a reference, the ligand will appear to be moving all over
the place.
Visualization of one of the trajctories is a must here (if you've not
already done that.) You can see what the ligand is doing. If it's
moving out of the pocket, there's nothing that cpptraj commands can do
after the fact.
If you want restraints to keep the ligand in the pocket, then need to be
relative restraints connecting the ligand and the protein, not
"absolute" ones that just keep the ligand (only) in one place.
Apologies if I'm off base here or mis-remembering things!
....dac
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Received on Mon Oct 05 2020 - 05:30:02 PDT
