COMPARISON OF QSAR AND MOLECULAR SIMILARITY APPROACHES FOR A STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF DHFR INHIBITORS DHFR INHIBITORS - QSAR AND MOLECULAR SIMILARITY APPROACHES

A comparison is made between classical QSAR approaches using multivari ate linear regression analysis and molecular similarity analysis (MSA) using inhibitors of dihydrofolate reductase (DHFR). A wide variety of descriptors derived directly from molecular structure are examined wi th both QSAR and MSA approaches. Three separate measures of molecular similarity are examined to determine how each compares with the QSAR m ethod in the context of the descriptors used. The QSAR method yielded a model with a R2 = 0.927 whose descriptors indicate that molecular si ze, shape and hydrogen bonding acceptor groups are important to activi ty. Molecular similarity approaches did not provide as good a model.Th e best correlation between pK(i) values and any given similarity metri c was obtained with the Tanimoto coefficient.