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

Calculated molecular properties from 3D molecular fields of interaction ene rgies 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 a nd exploited. 3D molecular fields can be obtained from ab initio, semiempir ical or molecular mechanics levels of calculation. The newly developed proc edure called VolSurf is able to compress the relevant information present i n 3D maps into a few descriptors characterised by the simplicity of their u se 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 de scriptors and models of structure-permeation relationships. The VolSurf pro cedure, which was originally designed to handle a medium amount of data, ca n easily be applied to problems of large size such as bioisostere databases , CombyChem databases and related approaches. (C) 2000 Elsevier Science B.V . All rights reserved.