Hello Debarati,
I can see that fluctuations are dependent on lambda value. When I was
doing TI calculations I did not used constraints for ligand and it
always left binding site at high lambdas, although most of ligand was
not part of TI region. This is not your case, but it might be pulled
back by applied restrains. With help of people from mailing list, we
found out that Berendsen barostat is not compatible with TI, so using
Monte Carlo barostat or NVT ensemble was the solution. So if you are
using Berendsen barostat you might consider change to Monte Carlo.
Juraj
On 05. 10. 20 14:16, Debarati DasGupta wrote:
> 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
>
>
>
>
>
> Sent from Mail<https://go.microsoft.com/fwlink/?LinkId=550986> for Windows 10
>
> 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 - 06:00:03 PDT
