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Computational Studies on Acetylcholinesterases

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...

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Autores principales: Xu, Yechun, Cheng, Shanmei, Sussman, Joel L., Silman, Israel, Jiang, Hualiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152020/
https://www.ncbi.nlm.nih.gov/pubmed/28796192
http://dx.doi.org/10.3390/molecules22081324
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author Xu, Yechun
Cheng, Shanmei
Sussman, Joel L.
Silman, Israel
Jiang, Hualiang
author_facet Xu, Yechun
Cheng, Shanmei
Sussman, Joel L.
Silman, Israel
Jiang, Hualiang
author_sort Xu, Yechun
collection PubMed
description 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.
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spelling pubmed-61520202018-11-13 Computational Studies on Acetylcholinesterases Xu, Yechun Cheng, Shanmei Sussman, Joel L. Silman, Israel Jiang, Hualiang Molecules Review 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. MDPI 2017-08-10 /pmc/articles/PMC6152020/ /pubmed/28796192 http://dx.doi.org/10.3390/molecules22081324 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Xu, Yechun
Cheng, Shanmei
Sussman, Joel L.
Silman, Israel
Jiang, Hualiang
Computational Studies on Acetylcholinesterases
title Computational Studies on Acetylcholinesterases
title_full Computational Studies on Acetylcholinesterases
title_fullStr Computational Studies on Acetylcholinesterases
title_full_unstemmed Computational Studies on Acetylcholinesterases
title_short Computational Studies on Acetylcholinesterases
title_sort computational studies on acetylcholinesterases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152020/
https://www.ncbi.nlm.nih.gov/pubmed/28796192
http://dx.doi.org/10.3390/molecules22081324
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