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Modeling of the metallo-beta-lactamase from B. fragilis: structural and dynamic effects of inhibitor binding
F R Salsbury1, M F Crowley, C L Brooks
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
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.
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