Molecular fields in quantitative structure–permeation relationships: the VolSurf approach

Abstract

Abstract Calculated molecular properties from 3D molecular fields of interaction energies have become a valuable approach to correlate 3D molecular structures with physicochemical and pharmacodynamic properties. In contrast, their use in correlations with pharmacokinetic properties is still poorly explored and exploited. 3D molecular fields can be obtained from ab initio, semiempirical or molecular mechanics levels of calculation. The newly developed procedure called VolSurf is able to compress the relevant information present in 3D maps into a few descriptors characterised by the simplicity of their use and interpretation. These descriptors can be quantitatively compared and used to build multivariate models correlating 3D molecular structures with biological responses. The VolSurf procedure is applied here to generate descriptors and models of structure–permeation relationships. The VolSurf procedure, which was originally designed to handle a medium amount of data, can easily be applied to problems of large size such as bioisostere databases, CombyChem databases and related approaches.