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 informat ion about size, shape and electrostatic distribution of a molecule. More re cently they were enriched introducing new molecular surface properties rela ted 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 compou nds, and iii) pK(a) values of 15 substituted imidazoles. PLS regressions we re in attempt to derived and validated through cross-validation, repeated s crambling of the response variables, and test set predictions. The analysis of PLS models showed that MS-WHIM provided meaningful structure-property c orrelations: i) q(2) = 0.709, ii) q(2) = 0.797, and iii) q(2) = 0.728. Hydr ogen bonding capacity and hydrophobicity played a significant role and cons iderably improved the results. MS-WHIM descriptors, due to their holistic c haracter, appear to be usefully applicable to a wide variety of chemical an d biological problems.