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Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model

[Image: see text] Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme–substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively u...

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Autores principales: Lu, Chenlin, Peng, Xue, Lu, Diannan, Liu, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203684/
https://www.ncbi.nlm.nih.gov/pubmed/32391467
http://dx.doi.org/10.1021/acsomega.9b04432
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author Lu, Chenlin
Peng, Xue
Lu, Diannan
Liu, Zheng
author_facet Lu, Chenlin
Peng, Xue
Lu, Diannan
Liu, Zheng
author_sort Lu, Chenlin
collection PubMed
description [Image: see text] Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme–substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) combined with Markov-state models (MSMs) implemented in pyEMMA was proposed to simulate diffusion pathways of 4-nitrophenyl ester (4NPE), a commonly used substrate, from the surface into the active site of CALB. Six important metastable conformations of CALB were identified in the diffusion process, including a closed state. An induced-fit mechanism incorporating multiple pathways with molecular information was proposed, which might find unprecedented applications for the rational design of lipase for green catalysis.
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spelling pubmed-72036842020-05-08 Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model Lu, Chenlin Peng, Xue Lu, Diannan Liu, Zheng ACS Omega [Image: see text] Profiling substrate diffusion pathways with kinetic information, which accounts for the dynamic nature of enzyme–substrate interaction, can enable molecular reengineering of enzymes and process optimization of enzymatic catalysis. Candida antarctica lipase B (CALB) is extensively used for producing various chemicals because of its rich catalytic mechanisms, broad substrate spectrum, thermal stability, and tolerance to organic solvents. In this study, an all-atom molecular dynamics (MD) combined with Markov-state models (MSMs) implemented in pyEMMA was proposed to simulate diffusion pathways of 4-nitrophenyl ester (4NPE), a commonly used substrate, from the surface into the active site of CALB. Six important metastable conformations of CALB were identified in the diffusion process, including a closed state. An induced-fit mechanism incorporating multiple pathways with molecular information was proposed, which might find unprecedented applications for the rational design of lipase for green catalysis. American Chemical Society 2020-04-23 /pmc/articles/PMC7203684/ /pubmed/32391467 http://dx.doi.org/10.1021/acsomega.9b04432 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Lu, Chenlin
Peng, Xue
Lu, Diannan
Liu, Zheng
Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title_full Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title_fullStr Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title_full_unstemmed Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title_short Global and Kinetic Profiles of Substrate Diffusion in Candida antarctica Lipase B: Molecular Dynamics with the Markov-State Model
title_sort global and kinetic profiles of substrate diffusion in candida antarctica lipase b: molecular dynamics with the markov-state model
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203684/
https://www.ncbi.nlm.nih.gov/pubmed/32391467
http://dx.doi.org/10.1021/acsomega.9b04432
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