[Dock-fans] Docking with metal ions

John Irwin jir322 at gmail.com
Thu Jan 19 09:05:51 PST 2012


Hi Jose

My suggestion is to make the metal part of the receptor, even if you
don't think of it that way.  Two reasons:  1) the residues on the
protein that bind the metal are not limitless. Enumerate the limited
possibilities. 2) forcefields for ligands assume a limited range of
atoms, usually C, N, O, F, P, S, Cl, Br, I, H.  For instance, B and
even Si are often poorly supported.  Metals are in my experience not
well modeled by the force fields usually used in drug discovery
software.

John


On Thu, Jan 19, 2012 at 2:12 AM, Jose R. Valverde
<jrvalverde at cnb.csic.es> wrote:
> Dear all,
>
>        besides the problems in my previous message, I am also trying
> to dock a molecule that is normally associated with a metal ion. My
> problem is how to get Zou GB/SA scores or estimate binding affinity.
>
>        The problem is that the ion should be placed wherever the ligand
> docks, i. e. always relative to the ligand pose, as it is not normally
> coupled to the enzyme, but the ligand. So docking should be done with
> the ion included in the ligand.
>
>        I do get the primary conformers using a grid score, but when
> they are minimized and rescored with Zou GB/SA I keep getting weird
> results (likely due to the presence of Mg++ in the ligand). Although
> I do not get these errors with Hawkins GB/SA or PB/SA, I'm worried
> the results may be wrong as well.
>
>        Something similar happens with Amber score: I cannot generate
> a topology for the ligand+ion (I tried SwissParam, ATB,..) and
> so the Amber method refuses to work.
>
>        Can anybody suggest any good alternative approach?
>
>                                j
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