title: BioGPS descriptors for rational engineering of enzyme promiscuity and structure based bioinformatic analysis.
abstract: A new bioinformatic methodology was developed founded on the Unsupervised Pattern Cognition Analysis of GRID-based BioGPS descriptors (Global Positioning System in Biological Space). The procedure relies entirely on three-dimensional structure analysis of enzymes and does not stem from sequence or structure alignment. The BioGPS descriptors account for chemical, geometrical and physical-chemical features of enzymes and are able to describe comprehensively the active site of enzymes in terms of "pre-organized environment" able to stabilize the transition state of a given reaction. The efficiency of this new bioinformatic strategy was demonstrated by the consistent clustering of four different Ser hydrolases classes, which are characterized by the same active site organization but able to catalyze different reactions. The method was validated by considering, as a case study, the engineering of amidase activity into the scaffold of a lipase. The BioGPS tool predicted correctly the properties of lipase variants, as demonstrated by the projection of mutants inside the BioGPS "roadmap".
authors.affiliation: Laboratory of Applied and Computational Biocatalysis, Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Trieste (TS), Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Ferrario
authors.affiliation: Laboratory for Chemometrics and Molecular Modeling, Dipartimento di Chimica, Biologia e Biotecnologie, Università degli Studi di Perugia, Perugia (PG), Italy.
authors.forename: Lydia
authors.initials: L
authors.lastname: Siragusa
authors.affiliation: Laboratory of Applied and Computational Biocatalysis, Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Trieste (TS), Italy.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ebert
authors.affiliation: Molecular Discovery Limited, Middlesex, London, United Kingdom.
authors.forename: Massimo
authors.initials: M
authors.lastname: Baroni
authors.affiliation: Laboratory of Applied and Computational Biocatalysis, Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Trieste (TS), Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Foscato
authors.affiliation: Laboratory for Chemometrics and Molecular Modeling, Dipartimento di Chimica, Biologia e Biotecnologie, Università degli Studi di Perugia, Perugia (PG), Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
authors.affiliation: Laboratory of Applied and Computational Biocatalysis, Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, Trieste (TS), Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gardossi
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057005:Bioengineering; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D008049:Lipase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D015203:Reproducibility of Results
chemical_list: D008049:Lipase; D000581:Amidohydrolases; C019665:amidase