title: Structure-based design of small-molecule protein-protein interaction modulators: the story so far.
abstract: As the pivotal role of protein-protein interactions in cell growth, transcriptional activity, intracellular trafficking, signal transduction and pathological conditions has been assessed, experimental and in silico strategies have been developed to design protein-protein interaction modulators. State-of-the-art structure-based design methods, mainly pharmacophore modeling and docking, which have succeeded in the identification of enzyme inhibitors, receptor agonists and antagonists, and new tools specifically conceived to target protein-protein interfaces (e.g., hot-spot and druggable pocket prediction methods) have been applied in the search for small-molecule protein-protein interaction modulators. Many successful applications of structure-based design approaches that, despite the challenge of targeting protein-protein interfaces with small molecules, have led to the identification of micromolar and submicromolar hits are reviewed here.
authors.affiliation: D3-Computation, Istituto Italiano di Tecnologia, Via Morego 30, I-16163 Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Falchi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Caporuscio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D000818:Animals; D003198:Computer Simulation; D062313:Databases, Pharmaceutical; D015195:Drug Design; D006801:Humans; D060066:Protein Interaction Maps / Q000187:drug effects*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries