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4885726 
Journal Article 
Calculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/Water 
Bannan, CC; Calabró, G; Kyu, DY; Mobley, DL 
2016 
Yes 
Journal of Chemical Theory and Computation
ISSN: 1549-9618
EISSN: 1549-9626 
12 
8 
4015-4024 
English 
27434695 
WOS:000381320200052 
Partition coefficients describe how a solute is distributed between two immiscible solvents. They are used in drug design as a measure of a solute's hydrophobicity and a proxy for its membrane permeability. We calculate partition coefficients from transfer free energies using molecular dynamics simulations in explicit solvent. Setup is done by our new Solvation Toolkit which automates the process of creating input files for any combination of solutes and solvents for many popular molecular dynamics software packages. We calculate partition coefficients between octanol/water and cyclohexane/water with the Generalized AMBER Force Field (GAFF) and the Dielectric Corrected GAFF (GAFF-DC). With similar methods in the past we found a root-mean-squared error (RMSE) of 6.3 kJ/mol in hydration free energies which would correspond to an error of around 1.6 log units in partition coefficients if solvation free energies in both solvents were estimated with comparable accuracy. Here we find an overall RMSE of about 1.2 log units with both force fields. Results from GAFF and GAFF-DC seem to exhibit systematic biases in opposite directions for calculated cyclohexane/water partition coefficients.