title: Modeling of the metallo-beta-lactamase from B. fragilis: structural and dynamic effects of inhibitor binding.
abstract: The structure and dynamics of an inhibitor-bound complex of the metallo-beta-lactamase from Bacteroides fragilis are studied by using molecular dynamics. A search of the conformational space was performed to obtain three distinct models of the complex, which were then subjected to solvated molecular dynamics. A solvated molecular dynamics study of the apo protein was performed to serve as a baseline for comparison with the bound simulations. We find loop conformation changes due to binding as well as a decrease in flexibility of the protein as a whole and especially in the major loop of the beta-lactamase. We report the structural and dynamical features of the inhibitor-bound and apo models, as well as experimentally measurable quantities, which should be capable of distinguishing the two binding modes we have determined.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Salsbury
authors.forename: M F
authors.initials: MF
authors.lastname: Crowley
authors.forename: C L
authors.initials: CL
authors.lastname: Brooks
mesh_terms: D001059:Apoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001441:Bacteroides fragilis / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D004795:Enzyme Stability; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents / Q000378:metabolism; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001059:Apoproteins; D004791:Enzyme Inhibitors; D012997:Solvents; D013844:Thiazoles; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases