BROWN RD, MARTIN YC

Pharmaceutical Products Division, Abbott Laboratories, D47E/AP10, 100 Abbott Park Road, Abbott Park, Illinois 60064-3500

An evaluation of a variety of structure-based clustering methods for use in compound selection is presented. The use of MACCS, Unity and Daylight 2D descriptors; Unity 3D rigid and flexible descriptors and two in-house 3D descriptors based on potential pharmacophore points are considered. The use of Ward's and group-average hierarchical agglomerative, Guenoche hierarchical divisive, and Jarvis-Patrick nonhierarchical clustering methods are compared. The results suggest that 2D descriptors and hierarchical clustering methods are best at separating biologically active molecules from inactives, a prerequisite for a good compound selection method. In particular, the combination of MACCS descriptors and Ward's clustering was optimal.

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES,36,1996,572-584