Drug design using comparative molecular surface analysis

Abstract

Chemists have eagerly extended a concept of shape into the molecular scale in an attempt to explain molecular effects. Although the molecular surface that shapes a molecule is a fuzzy category, which makes important theoretical problems with its precise interpretation, shape analysis appears to be an efficient method providing an explanation for a variety of effects. Comparative molecular surface analysis (CoMSA) is a three-dimensional quantitative structure–activity relationship (3D QSAR) method used for the comparison of molecular surfaces and shapes. In this review, the authors demonstrate that 3D QSAR basically works as a visualisation tool that investigates molecular similarity and indicates pharmacophoric sites. In this context, CoMSA that is based on the Kohonen self-organising maps that allow the projection of three-dimensional molecular data into two-dimensional maps without topological distortion has an important advantage over the traditional 3D QSAR methods. However, It should be remembered that the majority of the 3D QSAR limitations are still important for this technique and consequently a strategy to use the molecular data to produce drugs in this way still maps a ‘far and bumpy road’.