Molmaker: De Novo Generation Of 3d Databases For Use In Drug Design

A program, MOLMAKER, is described which, in conjunction with a 2D-3D conversion program and 3D database software, can generate de novo 3D databases to aid in drug design. MOLMAKER is based upon graph-theoretical techniques for vertex degree set generation and constructive enumeration of molecular graphs. The generated molecular graphs are then functionalised in a probabilistic manner but in accordance with various constraints specified by the user. The resulting connection tables can be converted into 3D structures by commercial software and loaded into a 3D database for pharmacophore searching. The utility of MOLMAKER is illustrated by two examples of interest from the recent scientific literature: the design of novel protein kinase C agonists and of a bridging ligand for cyclophilin-calcineurin.