GASP

Overview

GASP™ performs pharmacophore elucidation without requiring prior knowledge of pharmacophore elements or constraints. Using a genetic algorithm, GASP automatically allows conformational flexibility and maps features among molecules.

In the absence of a three-dimensional receptor structure, a model of the active site can be inferred from the ligands that bind to it. Key factors in developing such a model are the determination of functional groups essential for binding, their correspondence from one ligand to another, and the common spatial arrangement of these groups when bound to the receptor. GASP (Genetic Algorithm Similarity Program) employs a genetic algorithm for determining the correspondence between functional groups in different molecules and the alignment of these groups in a common geometry for receptor binding.

GASP Brochure (503k)

Two angiotensin II receptor antagonists (2D degree view, left) and one of their alignments determined by GASP (stereo view, right). Pharmacophore elements are represented as purple spheres and include rings and receptor hydrogen bond sites.

Key Benefits

• Allows full conformational flexibility of ligands, unlike methods that are limited to a pre-computed set of rigid conformers.
• Requires no advance knowledge of key functional groups or predefined correspondences between functional groups in different ligands.
• Automatically identifies rotatable bonds and key pharmacophore features. The only input required is a set of molecules.
• Intermolecular constraints can force correspondence between specific functional groups.