title: SPILLO-PBSS: detecting hidden binding sites within protein 3D-structures through a flexible structure-based approach.
abstract: The study reports a flexible structure-based approach aimed at identifying binding sites within target proteins starting from a well-defined reference binding site. The method, named SPILLO potential binding sites searcher (SPILLO-PBSS), includes a suitably designed tolerance which allows an efficient recognition of the potential binding sites regardless of both involved residues and protein conformation. Hence, the proposed method overcomes the rigidity which affects the available approaches and which prevents a proper analysis of distorted binding sites. We apply SPILLO-PBSS to several test cases, including the search for the guanosine diphosphate binding site in distorted H-Ras proteins and the identification of acetylcholine binding proteins from among a library of heterogeneous resolved proteins. Tests are also performed to compare SPILLO-PBSS with other related and available methods. The encouraging results confirm the notable potentialities of this approach and lay the foundation for its use to analyze and predict target proteins on a proteome-wide scale.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, 2, 20126, Milan, Italy; Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, 20133, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Domizio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vitriolo
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pedretti
mesh_terms: D000109:Acetylcholine / Q000737:chemistry*; D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology; D006153:Guanosine Diphosphate / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D020543:Proteome; D012984:Software
chemical_list: D011506:Proteins; D020543:Proteome; D006153:Guanosine Diphosphate; D000109:Acetylcholine
keywords: binding site detection; drug repositioning; molecular recognition; off-target proteins; protein druggability