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Molecular dynamics simulations of human butyrylcholinesterase
Author(s) -
Suárez Dimas,
Field Martin J.
Publication year - 2005
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.20398
Subject(s) - catalytic triad , molecular dynamics , chemistry , butyrylcholinesterase , active site , aqueous solution , residue (chemistry) , substrate (aquarium) , protein structure , binding site , crystallography , stereochemistry , catalysis , acetylcholinesterase , enzyme , computational chemistry , organic chemistry , biochemistry , aché , oceanography , geology
Herein, we present results from molecular dynamics (MD) simulations of the human butyrylcholinesterase (BuChE) enzyme in aqueous solution. Two configurations of the unbound form of BuChE differing in the presence or absence of a sodium ion inside the protein gorge were simulated for 10 and 5 ns, respectively. Besides complementing the structural information provided by X‐ray data, the MD simulations give insight into the structure of the native BuChE enzyme. For example, it is shown that: the nucleophilic Ser 198 residue and the various binding subsites in the BuChE catalytic cavity are readily accessible from the exterior of the protein; the presence of the sodium ion dynamically explores two different binding sites in the gorge leading to the active site and stabilizes the productive conformation of the Glu 325 /His 438 /Ser 198 catalytic triad; several long‐lived water bridges are fully integrated into the architecture of the active site; the positions of the residues at the rim of the gorge region display large deviations with respect to the crystal structure; and two side doors, constituted by residues situated at the tip of the acyl‐ and Ω‐loops, respectively, open wide enough to allow the passage of water molecules. In conclusion, we compare our theoretical results with those from previous work on mouse acetylcholinesterase and discuss their implications for substrate binding and catalysis in BuChE. Proteins 2005. © 2005 Wiley‐Liss, Inc.