Three-dimensional pharmacophoric pattern search using COMPASS: Nootropic agents

Abstract

This paper illustrates applicability of the COMPASS (Common Geometrical Pattern Search System) developed in our previous work for the analysis of the three-dimensional common structural features of drug molecules referred to as a pharmacophoric pattern. The three-dimensional common structural features of nootropics agents (rolziracetam, aniracetam and a tripeptide of Pro-Ala-Gly which is a vasopressin C-terminal analogue) have been examined using the system. Conformational analysis of the peptide was carried out in an exhaustive manner using the ECEPP/2 program, resulting in 232 stable conformations within 5 kcal/mol above the global energy minimum. Common geometrical pattern search between each of the conformers and rolziracetam, a rigid molecule, was performed with COMPASS. Seven different types of common geometrical patterns involving five constituent atoms were obtained with the consideration of their electronic environments. The resulting geometrical features were compared with those of an alternative COMPASS analysis between rolziracetam and aniracetam. The active conformation of the peptide and the pharmacophoric patterns of the present molecules are discussed, and the usefulness of our system for such work is also described.