title: Molecular descriptors for effective classification of biologically active compounds based on principal component analysis identified by a genetic algorithm.
abstract: We have evaluated combinations of 111 descriptors that were calculated from two-dimensional representations of molecules to classify 455 compounds belonging to seven biological activity classes using a method based on principal component analysis. The analysis was facilitated by application of a genetic algorithm. Using scoring functions that related the number of compounds in pure classes (i.e., compounds with the same biological activity), singletons, and mixed classes, effective descriptor sets were identified. A combination of only four molecular descriptors accounting for aromatic character, hydrogen bond acceptors, estimated polar van der Waals surface area, and a single structural key gave overall best results. At this performance level, approximately 91% of the compounds occurred in pure classes and mixed classes were absent. The results indicate that combinations of only a few critical descriptors are preferred to partition compounds according to their biological activity, at least in the test cases studied here.
authors.affiliation: New Chemical Entities, Inc., Bothell, Washington 98011, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D000465:Algorithms; D001685:Biological Factors / Q000145:classification / Q000494:pharmacology*; D003628:Database Management Systems; D008957:Models, Genetic
chemical_list: D001685:Biological Factors