While CoMFA and CoMSIA evaluate elds in the space surrounding the superimposed molecules under scrutiny, some other methods focus interest on explicit shape information. As indicated by Polanski et al. [363], shape is one of the fundamental categories used by the human brain for the perception and description of 3D objects. Molecular surfaces and volumes, although constituting only a conventional representation of molecular shapes, proved to be very useful to explain pharmacological effects such as drug-receptor interactions or molecular recognition processes. The inšuence of the steric interactions was long ago recognized as a determinant factor. Various approaches have been proposed.