Shape group studies of molecular similarity: relative shapes of Van der Waals and electrostatic potential surfaces of nicotinic agonists

Abstract In drug design, the usual strategy involves characterizing and comparing the shapes of molecules. We apply a simple method to accomplish this goal: determining the symmetry-independent shape groups (homology groups of algebraic topology) of a molecular surface. In this paper, we have adapted the method to describing the interrelation between Van der Waals and electrostatic potential surfaces. We describe rigorously the shape features in a series of molecules by using specific ranges of electrostatic potential over a Van der Waals surface. We consider a series of four nicotinic agonists as an example and discuss their expected activities as potential drugs on the basis of the shape similarities found.