Homology modeling, binding site identification, and docking study of human β-arrestin: an adaptor protein involved in apoptosis

Abstract

β-Arrestins are well-known negative regulators of G-protein-coupled receptors (GPCRs) signaling. The present study is aimed to build human β-arrestins 3D structures by homology modeling followed by identification and characterization of binding sites and there by assessing druggability of the proteins. Based upon BLAST results, bovine β-arrestin (PDB ID:1G4M) was considered as a template for homology modeling. Homology models were constructed using MODELLER program, refined and validated using PROCHECK in which >97 % of residues present in the favored regions of the Ramachandran plots. Since there are no co-ordinates of ligands available in the template, we used various binding site prediction algorithms to predict different binding pockets on the modeled proteins. To examine the response of proteins toward various apoptosis inducers, molecular docking study was carried out. The identification of 3D structures, binding sites for various signaling molecules will guide us designing molecular tools for therapeutic intervention that may prove useful in numerous disorders associated with β-arrestin-GPCRs signaling.