[gmx-users] FEP doubts

[David Mobley]

Diego,

> I am attempting to calculate binding free energy of a protein-ligand
> complex, but I'm facing some doubts.
> Is it possible to use the gromos96 force field instead of opls?

You can use any force field you want, in principle.

> Am I doing all the need type/typeB conversions just turning the atoms charge
> to 0 (zero)?

Turning the charges to zero would get you some of the electrostatic
component of binding. If you want a full binding free energy you will
need to do more.

> Should I do any modification in [bonds], [pairs], [angles] or [dihedrals]?
> Should I perform all these modifications just in the ligand topology or in
> the protein-ligand complex topology?

Are you trying to do the binding free energy of a single ligand to a
single protein? If so then you probably don't need to modify those
other sections. But you would if you were doing relative binding free
energies.

And yes, if you want a binding free energy, you have to mutate the
ligand when it's bound, too.

If you're trying to do absolute binding free energies, there are a
variety of nuances relating to the standard state and restraints. You
might want to start with a couple of the references on my web site
(http://www.dillgroup.ucsf.edu/~dmobley) and then look at the
references from those papers -- in particular the 2003 Borech paper
and the 1997 Gilson paper, among others.

David


> Thanks a lot,
> Diego.
>
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