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

[David Mobley]

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
504-383-3662
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