Re: Using FEP as non-disruptive mutation procedure

From: Jérôme Hénin (
Date: Mon Jun 27 2005 - 05:19:37 CDT


FEP may help you to grow a mutated sidechain in a protein. However, be aware
that in order to run an FEP simulation, you would have to build a hybrid
(so-called "dual topology") residue, for instance using psfgen to guess
coordinates for the new sidechain, then minimize it to obtain a resonable
starting structure. After the FEP simulation, you would still have to discard
the initial sidechain and convert the hybrid topology to the final one.

My feeling is that you would be better off building directly the mutated
structure using psfgen, and running a minimization followed by MD. Unless the
target amino-acid is much larger than the starting one, you shouldn't need to
grow it in a slow and progressive way.


On Monday 27 June 2005 00:10, Leonardo Sepulveda Durán wrote:
> Hello!!!
> I wanted to test the influence of some mutations on a protein. To
> create a mutant I used MODELLER. Nevertheless, modeller always change
> all the protein (althrough only a little) even in places far from the
> mutation site. That would be ok in most of the cases, neverless, I
> have seen differences in the dynamic behaviour far form the mutation
> site, and regarding what i said before i am not sure if it is an
> structural divergence due to the small differeces in nitial structure
> or must be an effect of mutation. I read FEP would be used to do free
> energy calculation of mutation, and I was wondering if FEP can then be
> used as a method mutate which only modifies nearby atoms, and not all
> the structure.
> Thanks
> Leonardo

Jérôme Hénin
Equipe de Dynamique des Assemblages Membranaires
Université Henri Poincaré / CNRS
Tel : (33) 3 83 68 43 95        Fax : (33) 3 83 68 43 87

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