ANCHOR: a web server and database for analysis of protein–protein interaction binding pockets for drug discovery

Abstract

ANCHOR is a web-based tool whose aim is to facilitate the analysis of protein–protein interfaces with regard to its suitability for small molecule drug design. To this end, ANCHOR exploits the so-called anchor residues, i.e. amino acid side-chains deeply buried at protein–protein interfaces, to indicate possible druggable pockets to be targeted by small molecules. For a given protein–protein complex submitted by the user, ANCHOR calculates the change in solvent accessible surface area (ΔSASA) upon binding for each side-chain, along with an estimate of its contribution to the binding free energy. A Jmol-based tool allows the user to interactively visualize selected anchor residues in their pockets as well as the stereochemical properties of the surrounding region such as hydrogen bonding. ANCHOR includes a Protein Data Bank (PDB) wide database of pre-computed anchor residues from more than 30 000 PDB entries with at least two protein chains. The user can query according to amino acids, buried area (SASA), energy or keywords related to indication areas, e.g. oncogene or diabetes. This database provides a resource to rapidly assess protein–protein interactions for the suitability of small molecules or fragments with bioisostere anchor analogues as possible compounds for pharmaceutical intervention. ANCHOR web server and database are freely available at http://structure.pitt.edu/anchor