Multi-phase Boltzmann weighting: accounting for local inhomogeneity in molecular simulations of water–octanol partition coefficients in the SAMPL6 challenge.

Accurately computing partition coefficients is a pivotal part of drug discovery. Specifically, octanol–water partition coefficients can provide information into hydrophobicity of drug-like molecules, as well as a de facto representation of membrane permeability. However, one challenge facing the computation of partition coefficients is the need to encapsulate various microscopic environments. These include areas of largely bulk solvent (i.e., either water or octanol) or regions where octanol is saturated with water or areas of higher salt concentration. Also, tautomeric effects require consideration. Thus, we present a Boltzmann weighting approach that incorporates transfer free energies across varying microscopic media, as well as varying tautomeric state, to compute partition coefficients in the SAMPL6 challenge. [ABSTRACT FROM AUTHOR]