Application of MS-WHIM Descriptors: 3. Prediction of Molecular Properties

MS-WHIM descriptors were developed in attempt to capture global 3D chemical information at molecular surface level. Initially, they contained information about size, shape and electrostatic distribution of a molecule. More recently they were enriched introducing new molecular surface properties related to hydrogen bonding capacity and hydrophobicity. This paper reports the application of expanded MS-WHIM descriptors to model: i) logP of 268 small organic molecules, ii) Caco-2 cell permeability of 17 heterogeneous compounds, and iii) pKa values of 15 substituted imidazoles. PLS regressions were derived and validated through cross-validation, repeated scrambling of the response variables, and test set predictions. The analysis of PLS models showed that MS-WHIM provided meaningful structure-property correlations: i) q2=0.709, ii) q2=0.797, and iii) q2=0.728. Hydrogen bonding capacity and hydrophobicity played a significant role and considerably improved the results. MS-WHIM descriptors, due to their holistic character, appear to be usefully applicable to a wide variety of chemical and biological problems.