[gmx-users] Metal-Protein interactions

[Justin Lemkul]

On 11/28/17 4:54 AM, RAHUL SURESH wrote:
> I am trying to simulate a metal-protein interaction using gromacs 2016
> package and charmm36 ff.
> I have prepared the initial pdb by performing an oniom calculations between
> protein and metal (at various positions) using gaussian 09 and chose the
> structure with maximum binding energy. The metal ion is bonded to oxygen
> atom of His residue. Having a look at gro file after each step
That's unusual; His typically coordinate metals via their delta or 
epsilon N atoms.

> (protein.gro, em.gro, nvt.groand npt.gro) the distance between metal  ion
> and the oxygen atom keeps increasing starting from 2.06 to 2.69. Over the
> course of simulations for 10ns, the metal ion is away from the protein.
>
> What can be done to have the metal ion restrained at its position? Or if I
> extend the simulation will the metal ion find its appropritae position
> during the course time?

Unlikely. This is a fundamental issue with classical mechanical force 
fields approximating ion interactions very poorly, particularly in the 
case of multivalent and/or transition metals. There are many effects 
like polarization and charge transfer that simply can't be modeled. You 
can apply distance restraints (or actual covalent bonds), NBFIX LJ 
parameters, etc. and that may be enough to preserve the binding pose. In 
reality, one would have to reparametrize any ligating residues because 
the charge distribution on the ion and anything coordinating it is not 
at all what the standard force field uses.

-Justin

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Justin A. Lemkul, Ph.D.
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Virginia Tech Department of Biochemistry

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