Small molecule hydration free energies in explicit solvent: An extensive test of fixed-charge atomistic simulations.

ABSTRACT: Using molecular dynamics free energy simulations with TIP3P explicit solvent, we compute the hydration free energies of 504 neutral small organic molecules and compare them to experiments. We find, first, good general agreement between the simulations and the experiments, with an RMS error of 1.24 kcal/mol over the whole set (i.e., about 2 kT) and a correlation coefficient of 0.89. Second, we use an automated procedure to identify systematic errors for some classes of compounds, and suggest some improvements to the force field. We find that alkyne hydration free energies are particularly poorly predicted due to problems with a Lennard-Jones well depth, and find that an alternate choice for this well depth largely rectifies the situation. Third, we study the non-polar component of hydration

SUBMITTER: Mobley DL 

PROVIDER: S-EPMC2701304 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature