title: Computational Insights into ADAMTS4, ADAMTS5 and MMP13 Inhibitor Selectivity.
abstract: The results obtained by means of Molecular Dynamics simulations and Multiway Explorative Data Analysis on ADAMTS4, ADAMTS5 and MMP13 complexed with Marimastat and two cis-1(S)2(R)-amino-2-indanol ligands suggest that determinant characteristics for ligand binding and selectivity among the three enzymes are to be found in the different protein conformation flexibility. Moreover, the role of the TS-domain in the inhibitor binding to ADAMTS enzymes has been investigated for the first time in this work. The results obtained suggest that the influence of the TS-domain on the S1' loop fluctuations of ADAMTS4 and ADAMTS5 could be exploited for the design of therapeutics for chronic osteoarthritis diseases.
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543.
authors.forename: Federico
authors.initials: F
authors.lastname: Filomia
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543.
authors.forename: Puneet
authors.initials: P
authors.lastname: Saxena
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543.
authors.forename: Caterina
authors.initials: C
authors.lastname: Durante
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543.|INFM-CNR National Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, 41100 Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: de Rienzo
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543.
authors.forename: Marina
authors.initials: M
authors.lastname: Cocchi
authors.affiliation: Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy tel: +39 059 2055091, fax: +39 059 373543. menziani@unimore.it.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Menziani
keywords: ADAMTSs; Inhibitors; MMP13; Molecular dynamics; Multiway analysis