Prediction of Chameleonic Efficiency

Prediction of chameleonic properties from environment-dependent conformational ensembles generated by molecular dynamics in explicit solvent is presented. This methodology yields predictive models of overall polarity (experimentally determined EPSA) and hydrogen bond donor exposure (experimentally measured delta log P_oct-tol) for 24 FDA-approved drug molecules. Two quantitative indices of chameleonic efficiency are introduced to aid drug designers striving to combine sufficient permeability and solubility.