QSAR and 3D QSAR in drug design .1. methodology

Classical QSAR methods describe structure-activity relationships in terms of physicochemical parameters and steric properties (Hansch analysis, extrathermodynamic approach), or certain structural features (Free Wilson analysis). 3D QSAR methods, especially comparative molecular field analysis, consider the three-dimensional structures and the binding modes of protein ligands. Quantitative similarity-activity relationships derive correlations between the similarities of individual compounds and their biological activities. Theory and methodology of these approaches are described here, together with the proper use of regression and partial least squares analyses for deriving quantitative structure-activity relationships. Part 2, to be published in the December issue, will address applications and problems.