QSAR AND 3D QSAR IN DRUG DESIGN .1. METHODOLOGY

Classical QSAR methods describe structure-activity relationships in te rms of physicochemical parameters and steric properties (Hansch analys is, extrathermodynamic approach), or certain structural features (Free Wilson analysis). 3D QSAR methods, especially comparative molecular f ield analysis, consider the three-dimensional structures and the bindi ng modes of protein ligands. Quantitative similarity-activity relation ships derive correlations between the similarities of individual compo unds and their biological activities. Theory and methodology of these approaches are described here, together with the proper use of regress ion and partial least squares analyses for deriving quantitative struc ture-activity relationships. Part 2, to be published in the December i ssue, will address applications and problems.