A Comprehensive Review of Cholinesterase Modeling and Simulation
The present article reviews published efforts to study acetylcholinesterase and butyrylcholinesterase structure and function using computer-based modeling and simulation techniques. Structures and models of both enzymes from various organisms, including rays, mice, and humans, are discussed to highl...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/4/580 |
| _version_ | 1797537599050481664 |
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| author | Danna De Boer Nguyet Nguyen Jia Mao Jessica Moore Eric J. Sorin |
| author_facet | Danna De Boer Nguyet Nguyen Jia Mao Jessica Moore Eric J. Sorin |
| author_sort | Danna De Boer |
| collection | DOAJ |
| description | The present article reviews published efforts to study acetylcholinesterase and butyrylcholinesterase structure and function using computer-based modeling and simulation techniques. Structures and models of both enzymes from various organisms, including rays, mice, and humans, are discussed to highlight key structural similarities in the active site gorges of the two enzymes, such as flexibility, binding site location, and function, as well as differences, such as gorge volume and binding site residue composition. Catalytic studies are also described, with an emphasis on the mechanism of acetylcholine hydrolysis by each enzyme and novel mutants that increase catalytic efficiency. The inhibitory activities of myriad compounds have been computationally assessed, primarily through Monte Carlo-based docking calculations and molecular dynamics simulations. Pharmaceutical compounds examined herein include FDA-approved therapeutics and their derivatives, as well as several other prescription drug derivatives. Cholinesterase interactions with both narcotics and organophosphate compounds are discussed, with the latter focusing primarily on molecular recognition studies of potential therapeutic value and on improving our understanding of the reactivation of cholinesterases that are bound to toxins. This review also explores the inhibitory properties of several other organic and biological moieties, as well as advancements in virtual screening methodologies with respect to these enzymes. |
| first_indexed | 2024-03-10T12:18:31Z |
| format | Article |
| id | doaj.art-968443cad3d14fc48e353285decb4c2e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T12:18:31Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-968443cad3d14fc48e353285decb4c2e2023-11-21T15:42:11ZengMDPI AGBiomolecules2218-273X2021-04-0111458010.3390/biom11040580A Comprehensive Review of Cholinesterase Modeling and SimulationDanna De Boer0Nguyet Nguyen1Jia Mao2Jessica Moore3Eric J. Sorin4Department of Chemistry & Biochemistry, California State University, Long Beach, CA 90840, USADepartment of Chemical Engineering, California State University, Long Beach, CA 90840, USADepartment of Chemical Engineering, California State University, Long Beach, CA 90840, USADepartment of Biomedical Engineering, California State University, Long Beach, CA 90840, USADepartment of Chemistry & Biochemistry, California State University, Long Beach, CA 90840, USAThe present article reviews published efforts to study acetylcholinesterase and butyrylcholinesterase structure and function using computer-based modeling and simulation techniques. Structures and models of both enzymes from various organisms, including rays, mice, and humans, are discussed to highlight key structural similarities in the active site gorges of the two enzymes, such as flexibility, binding site location, and function, as well as differences, such as gorge volume and binding site residue composition. Catalytic studies are also described, with an emphasis on the mechanism of acetylcholine hydrolysis by each enzyme and novel mutants that increase catalytic efficiency. The inhibitory activities of myriad compounds have been computationally assessed, primarily through Monte Carlo-based docking calculations and molecular dynamics simulations. Pharmaceutical compounds examined herein include FDA-approved therapeutics and their derivatives, as well as several other prescription drug derivatives. Cholinesterase interactions with both narcotics and organophosphate compounds are discussed, with the latter focusing primarily on molecular recognition studies of potential therapeutic value and on improving our understanding of the reactivation of cholinesterases that are bound to toxins. This review also explores the inhibitory properties of several other organic and biological moieties, as well as advancements in virtual screening methodologies with respect to these enzymes.https://www.mdpi.com/2218-273X/11/4/580acetylcholinesterasebutyrylcholinesterasedockingmolecular dynamicshydrolysismolecular recognition |
| spellingShingle | Danna De Boer Nguyet Nguyen Jia Mao Jessica Moore Eric J. Sorin A Comprehensive Review of Cholinesterase Modeling and Simulation Biomolecules acetylcholinesterase butyrylcholinesterase docking molecular dynamics hydrolysis molecular recognition |
| title | A Comprehensive Review of Cholinesterase Modeling and Simulation |
| title_full | A Comprehensive Review of Cholinesterase Modeling and Simulation |
| title_fullStr | A Comprehensive Review of Cholinesterase Modeling and Simulation |
| title_full_unstemmed | A Comprehensive Review of Cholinesterase Modeling and Simulation |
| title_short | A Comprehensive Review of Cholinesterase Modeling and Simulation |
| title_sort | comprehensive review of cholinesterase modeling and simulation |
| topic | acetylcholinesterase butyrylcholinesterase docking molecular dynamics hydrolysis molecular recognition |
| url | https://www.mdpi.com/2218-273X/11/4/580 |
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