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Modeling of the metallo‐β‐lactamase from B. fragilis : Structural and dynamic effects of inhibitor binding
Author(s) -
Salsbury Freddie R.,
Crowley Michael F.,
Brooks Charles L.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1110
Subject(s) - molecular dynamics , bacteroides fragilis , dynamics (music) , chemistry , flexibility (engineering) , biophysics , physics , computational chemistry , biology , biochemistry , mathematics , antibiotics , statistics , acoustics
The structure and dynamics of an inhibitor‐bound complex of the metallo‐β‐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 β‐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. Proteins 2001;44:448–459. © 2001 Wiley‐Liss, Inc.