Dear David, GMX users,
David Mobley wrote:
Ran,
I previously asked how to calculate the long range interactions between
charged particles simulated with PME:
http://www.gromacs.org/pipermail/gmx-users/2004-October/012627.html
I repeat the question here. If I want to calculate the LR Coulomb
interaction energy between say a protein and a ligand the normal
procedure would involve several mdrun -rerun runs: (1) with atoms
charged (2) with the charges on the protein neutralised (3) with the
charges on the ligand neutralised (4) with the charges on the solvent
neutralised. When the protein is charged, there will be a net charge in
the simulation shell in case (2). This net charged is corrected in PME
as implemented in GMX. In GMX 3.2.1, I could not account for the
correction, so the calculation wouldn't be exact (see the message
above). What's the situation in GMX 3.3.1?
Systems with net charge are run with a uniform neutralizing background
charge sincce they need to be neutral for PME. I don't have any idea
how to properly account for this, although I would like to. This isn't
just an issue for calculating interaction energies between, say, two
molecules -- one also has to deal with similar issues if one wants to
compute, say, the free energy of inserting or removing an ion.
The problem, as I see it, is that I can't figure out any way to
calculate the contribution to the energy (or free energy) of turning
on the neutralizing background charge, which one would need to
subtract off to get this right.
I guess what makes this tricky is that you are really talking about
the same problem I would have if I want to get an ion hydration free
energy: You want to be able to evaluate the long range electrostatic
interactions in a system that has net charge (a protein+ligand, where
the protein+ligand isn't neutral; it's only neutral when you add the
ions), so you really need to be able to do this with the neutralizing
background charge (which will let you do the sum) and then somehow
subtract off the energy of turning on the neutralizing background
charge, which you can't compute directly since your sum won't converge
if you turn it off.
Right.
Maybe there is some way to get this out of the right combination of
mdrun -rerun options. Can you be a bit more explicit about how you are
thinking you would get this if you did (1) through (4)? And what do
you mean by saying that this is the "normal procedure"? (Do you have a
reference on it?)
I was not accurate. E(LR) is the total PME energy, and the rest can be
extracted by neutralising selected groups. So the binding energy can
calculated from: E(LR)-E(sol-sol)- E(ligand-ligand)-
E(protein-protein)-E(solvent-ligand)-E(solvent-protein), where e.g.
E(sol-sol) can be calculated when the protein and the ligand are both
made uncharged. This still leaves us with the PME correction.
I think that deltaG calculations with charged particles and periodic
systems are much more difficult than the interaction energy, and I do
not deal with them.
Ran.
Please continue the discussion. I'm happy to help in any way I can,
but I just need to understand what you're thinking a bit better, and
I'm also not sure anyone knows how to do this yet (at least, I'm not
aware of anything that explains this).
One reference that seems useful that I don't completely understand yet
is this one:
Kastenholz, M. & Hunenberger, P.H.
Computation of methodology-independent ionic solvation free energies from
molecular simulations: II. The hydration free energy of the sodium
cation.
J. Chem. Phys., 124, 224501 (2006).
David Mobley
UCSF
Thanks,
Ran.
--
------------------------------------------------------
Ran Friedman
http://bioinfo.tau.ac.il/~ran
Laser Laboratory for Fast Reactions in Biology
Department of Biochemistry
Faculty of Life Sciences
Tel-Aviv University
Tel. +972-3-6409824
Fax. +972-3-6409875
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------------------------------------------------------
Ran Friedman
http://bioinfo.tau.ac.il/~ran
Laser Laboratory for Fast Reactions in Biology
Department of Biochemistry
Faculty of Life Sciences
Tel-Aviv University
Tel. +972-3-6409824
Fax. +972-3-6409875
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