Approaches for Calculating Solvation Free Energies and Enthalpies Demonstrated with an Update of the FreeSolv Database

Solvation
free energies can now be calculated precisely from molecular
simulations, providing a valuable test of the energy functions underlying
these simulations. Here we briefly review “alchemical”
approaches for calculating the solvation free energies of small, neutral
organic molecules from molecular simulations and illustrate these
approaches by applying them to calculate aqueous solvation free energies
(hydration free energies). These approaches use a nonphysical pathway
to compute free energy differences from a simulation or set of simulations
and appear to be a particularly robust and general-purpose approach
for this task. We also present an update (version 0.5) to our FreeSolv
database of experimental and calculated hydration free energies of
neutral compounds and provide input files in formats for several simulation
packages. This revision to FreeSolv provides calculated values generated
with a single protocol and software version rather than the heterogeneous
protocols used in the prior version of the database. We also further
update the database to provide calculated enthalpies and entropies
of hydration and some experimental enthalpies and entropies as well
as electrostatic and nonpolar components of solvation free energies.