Geometric manipulation of flexible ligands

Abstract

In recent years an effort has been made to supplement tradi­tional methods for drug discovery by computer-assisted “structure-based design.” The structure-based approach involves (among other issues) rea­soning about the geometry of drug molecules (or ligands) and about the different spatial conformations that these molecules can attain. This is a preliminary report on a set of tools that we are devising to assist the chemist in the drug design process. We describe our work on the fol­lowing three topics: (i) geometric data structures for representing and manipulating molecules; (ii) conformational analysis—searching for low- energy conformations; and (iii) pharmacophore identification—searching for common features among different ligands that exhibit similar activity.