Use of surface charges from DFT calculations to predict intestinal absorption.

A model for prediction of percent intestinal absorption (%Abs) of neutral molecules was developed based upon surface charges of the molecule calculated by density functional theory (DFT). The surface charges are decomposed into sigma moments which are correlated to a partition coefficient representing transfer of the molecule between water and the epithelial membrane. The model was built and tested using a data set of 241 drugs. It achieved an RMS deviation of 13% on a training set of 38 compounds as well as on a test set of 107 drugs for which the experimental data were classified as high quality. Property maps of the molecule, depicting which atoms contribute to or hinder absorption, are produced to aid drug design.