Re: FEP substrate transformation with common moiety

From: Jérôme Hénin (jhenin_at_ifr88.cnrs-mrs.fr)
Date: Sat Aug 28 2010 - 08:52:46 CDT

Sebastian,

Let me add one remark to Chris' reply: the best strategy also depends
on how different A and B are. If they are roughly the same size and
shape, and you expect a similar binding mode, you could use option B
(define separate topologies) and add restraints the keep A and B on
top of each other, but no restraints with respect to the binding site.
If both A and B bind strongly enough, then the intermediate stages
should stay bound as well. If the transformation is sampled for long
enough, you should see full relaxation from the equilibrium A-X
complex to equilibrium B-X. Ideally, what happens in FEP should be
compared with what is sampled in separate equilibrium simulations of
both complexes.

Cheers,
Jerome

On 28 August 2010 03:35, Sebastian Stolzenberg <s.stolzenberg_at_gmail.com> wrote:
> Dear All,
>
> I would like to use FEP to slowly transform one substrate A, bound to a
> protein in binding site X, into another substrate B bound to X, i.e. not
> considering the exact free energy value of this transformation.
>
> Initial and final substrates have a common moiety.
>
> I see two options:
> a) Define a FEP hybrid topology entry A2B with the joint common moiety
> b) Simply include A and B as two separate PDB entries, restrain B to A and
> to X
>
> Could anybody kindly share their experience what option might work better?
>
> Thank you very much,
> Best,
> Sebastian
>
>

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