[gmx-developers] decoupling in free energy calculations for binding

Berk Hess hess at cbr.su.se
Thu Jun 23 11:23:03 CEST 2011


You can manually set up the decoupling, but that's very tedious and 
error prone.
I think the best procedure would be to restrain using the pull code,
but I don't know if that's currently flexible enough to cover most cases.
If not, we should think about extend the functionality of the pull code.

I though the decoupled state is described somewhere in the manual.
It is a non-periodic state with pure Coulomb and LJ interactions without 
(unless you use couple-intramol).


On 06/23/2011 04:46 AM, David Mobley wrote:
> Hi,
> We're trying to do absolute binding free energy calculations using 
> Michael Shirts' latest free energy code (to be included in 4.6 if I 
> understand correctly; right now it's  a branch of 4.5). These require 
> using a restraint between the protein and the ligand, which currently 
> we're doing using virtual sites. I am interested in also doing these 
> calculations using "decoupling", wherein internal interactions of the 
> perturbed molecule (in this case the ligand) are retained. This 
> involves something like the following in the mdp file:
> couple-moltype            = MOL
> couple-lambda0            = vdw-coul
> couple-lambda1            = none
> couple-intramol           = no
> if, for example, the ligand is a molecule named 'MOL'.
> My question is this: Is there any way to get this to work when the 
> ligand and the protein are part of the same "molecule"? Specifically, 
> to have restraints betweeen the protein and the ligand (such as using 
> a virtual site) which are NECESSARY for absolute binding free energy 
> calculations, I must have the protein and ligand as part of the same 
> molecule (unless there's a workaround I'm not aware of). But to get 
> decoupling to work using the above I seem to need to have the protein 
> and ligand as separate molecules, suggesting they are incompatible. Is 
> there a workaround I'm not aware of?
> Also, on a related note -- when decoupling is done, what is the end 
> state for the decoupled object? Is it the decoupled object in gas 
> phase in a periodic system (interacting with copies of itself), or in 
> a nonperiodic system?
> Thanks!
> -- 
> David Mobley
> dmobley at gmail.com <mailto:dmobley at gmail.com>
> 504-383-3662

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