Geometrical Constraints for Ligand Positioning

Virginio Cantoni, Alessandro Gaggia, Riccardo Gatti, Luca Lombardi

Keywords: Protein-ligand interaction, active sites detection, Extended Gaussian Image, alignment of biological molecules, structural matching, mathematical morphology.

Abstract: The purpose of the activity here described is the morphological and subsequently the geometrical and topological analysis of the active sites in protein surfaces for protein-ligand docking. The approach follows a sequence of three steps: i) the solvent-excluded-surface is analyzed and segmented in a number of pockets and tunnels; ii) the candidate binding sites are detected through a structural matching of pockets and ligand, both represented through a suitable Extended Gaussian Image modality; iii) the loci of compatible positions of the ligand is identified through mathematical morphology. This representation of ligand and candidate binding pockets, the comparison of the morphological similarity and the identification of potential ligand docking are the novelties of this proposal.