title: Hot spots in protein-protein interfaces: towards drug discovery.
abstract: Identification of drug-like small molecules that alter protein-protein interactions might be a key step in drug discovery. However, it is very challenging to find such molecules that target interface regions in protein complexes. Recent findings indicate that such molecules usually target specifically energetically favored residues (hot spots) in protein-protein interfaces. These residues contribute to the stability of protein-protein complexes. Computational prediction of hot spots on bound and unbound structures might be useful to find druggable sites on target interfaces. We review the recent advances in computational hot spot prediction methods in the first part of the review and then provide examples on how hot spots might be crucial in drug design.
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey.
authors.forename: Engin
authors.initials: E
authors.lastname: Cukuroglu
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey.
authors.forename: H Billur
authors.initials: HB
authors.lastname: Engin
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey.
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey. Electronic address: okeskin@ku.edu.tr.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
mesh_terms: D019295:Computational Biology; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009154:Mutation; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: Drug design; Hot spot; Protein–protein interaction; Protein–protein interface