Understanding binding affinity and specificity of modular protein domains: A focus in ligand design for the polyproline-binding families Martínez Herrerías, José Cristóbal Castillo, Francisco Ruiz Sanz, Javier Murciano Calles, Javier Cámara-Artigas, Ana Luque Fernández, Irene EVH1 domains; GYF domains Ligand design Polyproline peptides Protein-protein interactions SH3 domains Structure/function relationships in protein domains UEV domains; WW domains 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. 2025-01-22T09:43:30Z 2025-01-22T09:43:30Z 2022-01-10 book part Martinez JC, Castillo F, Ruiz-Sanz J, Murciano-Calles J, Camara-Artigas A, Luque I. Understanding binding affinity and specificity of modular protein domains: A focus in ligand design for the polyproline-binding families. Adv Protein Chem Struct Biol. 2022;130:161-188. doi: 10.1016/bs.apcsb.2021.12.002. Epub 2022 Jan 10. PMID: 35534107. https://hdl.handle.net/10481/99939 https://doi.org/10.1016/BS.APCSB.2021.12.002 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier Inc.