title: Dynamical aspects of TEM-1 beta-lactamase probed by molecular dynamics.
abstract: The dynamical aspects of the fully hydrated TEM-1 beta-lactamase have been determined by a 5 ns Molecular Dynamics simulation. Starting from the crystallographic coordinates, the protein shows a relaxation in water with an overall root mean square deviation from the crystal structure increasing up to 0.17 nm, within the first nanosecond. Then a plateau is reached and the molecule fluctuates around an equilibrium conformation. The results obtained in the first nanosecond are in agreement with those of a previous simulation (Diaz et al., J. Am. Chem. Soc., (2003) 125, 672-684). The successive equilibrium conformation in solution shows an increased mobility characterized by the following aspects. A flap-like translational motion anchors the omega-loop to the body of the enzyme. A relevant part of the backbone dynamics implies a rotational motion of one domain relative to the other. The water molecules in the active site can exchange with different residence times. The H-bonding networks formed by the catalytic residues are frequently interrupted by water molecules that could favour proton transfer reactions. An additional simulation, where the aspartyl dyad D214-D233 was considered fully deprotonated, shows that the active site is destabilized.
authors.affiliation: Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universitá degli Studi, V. Vetoio, 67010, L'Aquila, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Roccatano
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sbardella
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Amicosante
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bossa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Nola
authors.forename: Fernando
authors.initials: F
authors.lastname: Mazza
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D011522:Protons; D014867:Water; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1