On Tue, Nov 27, 2018, Braden Kelly wrote:
>
>Amber documentation covers Free Energy calculations, such as
>thermodynamic integration and using other methods such as BAR. It
>independently discusses QM/MM as well. However free energy calculations,
>specifically alchemical changes in which a molecule is decoupled from the
>system, or mutated into another molecule, using a lambda parameter that
>changes from 0 to 1 or vice versa, are not discussed in the context of
>QM/MM.
In sander, one *can* put TI and QM/MM together; special care would need to
be taken with softcore LJ terms (and use of softcore electrostatics would
not work at all.) I don't see any way to use BAR (but I might be missing
something).
The downside is that one needs to be able to afford the QM/MM
calculation in the first place, and to carry out significant simulations
at a variety of lambda points. This requires a *lot* of computation,
unless you happen to have a system where semiempirical or DFTB
Hamiltonians are accurate enough for your purposes.
It is for this reason that a big portion of current research in this
area explores the suggestion made by Brian: carry out a transformation
at the MM level, then apply MM->QM/MM "corrections" at the end points.
In favorable circumstances, this can involve many fewer QM calculations,
which generally are by far the most expensive parts of the simulation.
>I am specifically interested in hydration free energies of small (<50
>atoms) organic molecules.
If you want just the hydration free energies, you might be better off
which implicit solvent models, such as the various flavors of
"Minnesota" models (such as SMx and its many variants.) Using explicit
solvent models (and a program like Amber) would mainly be of interest if
you want the difference in solvation energy between two environments,
say pure water, and a protein/water environment.
....good luck....dac
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Received on Tue Nov 27 2018 - 19:00:01 PST
