Understanding binding affinity and specificity of modular protein domains: A focus in ligand design for the polyproline-binding families

Abstract

Within the modular protein domains there are five families that recognize proline-rich sequences: SH3, WW, EVH1, GYF and UEV domains. This chapter reviews the main strategies developed for the design of ligands for these families, including peptides, peptidomimetics and drugs. We also describe some studies aimed to understand the molecular reasons responsible for the intrinsic affinity and specificity of these domains.

Keywords: EVH1 domains; GYF domains; Ligand design; Polyproline peptides; Protein-protein interactions; SH3 domains; Structure/function relationships in protein domains; UEV domains; WW domains.