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Biophys J. 2003 Oct;85(4):2267-72.

The dynamics of ligand barrier crossing inside the acetylcholinesterase gorge.

Author information

1
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093-0365, USA. jbui@mccammon.ucsd.edu

Abstract

The dynamics of ligand movement through the constricted region of the acetylcholinesterase gorge is important in understanding how the ligand gains access to and is released from the active site of the enzyme. Molecular dynamics simulations of the simple ligand, tetramethylammonium, crossing this bottleneck region are conducted using umbrella potential sampling and activated flux techniques. The low potential of mean force obtained is consistent with the fast reaction rate of acetylcholinesterase observed experimentally. From the results of the activated dynamics simulations, local conformational fluctuations of the gorge residues and larger scale collective motions of the protein are found to correlate highly with the ligand crossing.

PMID:
14507691
PMCID:
PMC1303452
DOI:
10.1016/S0006-3495(03)74651-7
[Indexed for MEDLINE]
Free PMC Article
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