[gmx-users] simulation with ligand at the active site

[Mark Abraham]

On 4/28/2011 3:21 PM, onetwo wrote:
> Hello Users,
>
> I have a query regarding simulation with the ligand.
>
> In my protein there are two ligands, one of them (coenzyme) is from the
> crystal data, and other I have docked at the active site, while docking
> it is showing good interaction with all the active site residues very
> well.
> I used GROMOS96 43a1 force field, and got the topology file made from
> prodrg beta, using GROMOS 96.1 for both the ligands.
> while doing equilibration I did, brendenson coupling on like
> ; Berendsen temperature coupling is on in two groups
> Tcoupl = V-rescale

You used V-rescale (per the command), not Berendsen (per the comment). 
However, that's not a problem.

> tc-grps = Protein Non-Protein
> tau_t = 0.1 0.1
> ref_t = 300 300
>
> and in MD simulation also
> ; Berendsen temperature coupling is on in two groups
> Tcoupl = V-rescale
> tc-grps = Protein Non-Protein
> tau_t = 0.1 0.1
> ref_t = 300 300
>
> But after 1ns equibiration, one of the ligand (the one which I docked)
> is going away from the active site and then I ran it for 4 ns further,
> it has gone more far from the cavity. Following is the link to the 
> snapshot of the ligand at different time.
>
> https://picasaweb.google.com/118389174994698260649/Md_complex?authkey=Gv1sRgCMis2qry3cGj7AE#5600499037480314402
>
> I want to ask if the change in the
> position of ligand is justified with the parameters i have taken or it
> if i have done something wrong?

It is well known (and published) that PRODRG can produce garbage 
charges. Perhaps you have evidence of that here.

If you expect your ligand to stay bound, it may make more sense to 
T-couple it with the protein, using a custom index group, then to couple 
it with solvent. However, I'd look at my charges first.

Mark