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Erratum published on 6 September 2017, see Molecules 2017, 22(9), 1486.

Open AccessFeature PaperReview
Molecules 2017, 22(8), 1324;

Computational Studies on Acetylcholinesterases

CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China
Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot 76100, Israel
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Author to whom correspondence should be addressed.
Received: 10 July 2017 / Revised: 7 August 2017 / Accepted: 7 August 2017 / Published: 10 August 2017
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Functions of biomolecules, in particular enzymes, are usually modulated by structural fluctuations. This is especially the case in a gated diffusion-controlled reaction catalyzed by an enzyme such as acetylcholinesterase. The catalytic triad of acetylcholinesterase is located at the bottom of a long and narrow gorge, but it catalyzes the extremely rapid hydrolysis of the neurotransmitter, acetylcholine, with a reaction rate close to the diffusion-controlled limit. Computational modeling and simulation have produced considerable advances in exploring the dynamical and conformational properties of biomolecules, not only aiding in interpreting the experimental data, but also providing insights into the internal motions of the biomolecule at the atomic level. Given the remarkably high catalytic efficiency and the importance of acetylcholinesterase in drug development, great efforts have been made to understand the dynamics associated with its functions by use of various computational methods. Here, we present a comprehensive overview of recent computational studies on acetylcholinesterase, expanding our views of the enzyme from a microstate of a single structure to conformational ensembles, strengthening our understanding of the integration of structure, dynamics and function associated with the enzyme, and promoting the structure-based and/or mechanism-based design of new inhibitors for it. View Full-Text
Keywords: acetylcholinesterase; computational modeling and simulation; active-site gorge; ligand trafficking; oligomer; catalytic reaction mechanism acetylcholinesterase; computational modeling and simulation; active-site gorge; ligand trafficking; oligomer; catalytic reaction mechanism

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Xu, Y.; Cheng, S.; Sussman, J.L.; Silman, I.; Jiang, H. Computational Studies on Acetylcholinesterases. Molecules 2017, 22, 1324.

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