title: On the structural affinity of macromolecules with different biological properties: molecular dynamics simulations of a series of TEM-1 mutants.
abstract: Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical-biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment.
authors.affiliation: Dipartimento di Scienze Fisiche e Chimiche, Universita' degli Studi di l'Aquila, Via Vetoio snc, 67100 Coppito (AQ), Italy.
authors.forename: Alessia Di
authors.initials: AD
authors.lastname: Giampaolo
authors.forename: Fernando
authors.initials: F
authors.lastname: Mazza
authors.forename: Isabella
authors.initials: I
authors.lastname: Daidone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Amicosante
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Perilli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
mesh_terms: D020134:Catalytic Domain; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D013816:Thermodynamics; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics
chemical_list: D001618:beta-Lactamases; C034413:beta-lactamase TEM-1
keywords: ED; ESBL; IRT; MD; Molecular dynamics; Point mutations; Structural and dynamical properties; TEM-1 betalactamases; essential dynamics; extended-spectrum beta-lactamases; inhibitor-resistant TEM; molecular dynamics