Automated Topology Builder Version 3.0: Prediction of Solvation Free Enthalpies in Water and Hexane

The ability of atomic
interaction parameters generated using the Automated Topology Builder
and Repository version 3.0 (ATB3.0) to predict experimental hydration
free enthalpies (ΔGwater) and solvation
free enthalpies in the apolar solvent hexane (ΔGhexane) is presented. For a validation set of 685 molecules
the average unsigned error (AUE) between ΔGwater values calculated using the ATB3.0 and experiment
is 3.8 kJ·mol–1. The slope of the line of best
fit is 1.00, the intercept −1.0 kJ·mol–1, and the R2 0.90. For the more restricted
set of 239 molecules used to validate OPLS3 (J. Chem. Theory Comput. 2016, 12, 281−296, DOI: 10.1021/acs.jctc.5b00864)
the AUE using the ATB3.0 is just 2.7 kJ·mol–1 and the R2 0.93. A roadmap for further
improvement of the ATB parameters is presented together with a discussion
of the challenges of validating force fields against the available
experimental data.