Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478161" target="_blank" >RIV/61388963:_____/17:00478161 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.jpcb.7b03102" target="_blank" >http://dx.doi.org/10.1021/acs.jpcb.7b03102</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.7b03102" target="_blank" >10.1021/acs.jpcb.7b03102</a>
Alternative languages
Result language
angličtina
Original language name
Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent
Original language description
Enzymes are widely used in nonaqueous solvents to catalyze non-natural reactions. While experimental measurements showed that the solvent nature has a strong effect on the reaction kinetics, the molecular details of the catalytic mechanism in nonaqueous solvents have remained largely elusive. Here we study the transesterification reaction catalyzed by the paradigm subtilisin Carlsberg serine protease in an organic apolar solvent. The rate-limiting acylation step involves a proton transfer between active-site residues and the nucleophilic attack of the substrate to form a tetrahedral intermediate. We design the first coupled valence-bond state model that simultaneously describes both reactions in the enzymatic active site. We develop a new systematic procedure to parametrize this model on high-level ab initio QM/MM free energy calculations that account for the molecular details of the active site and for both substrate and protein conformational fluctuations. Our calculations show that the reaction energy barrier changes dramatically with the solvent and protein conformational fluctuations. We find that the mechanism of the tetrahedral intermediate formation during the acylation step is similar to that determined under aqueous conditions, and that the proton transfer, and nucleophilic attack reactions occur concertedly. We identify the reaction coordinate to be mostly due to the rearrangement of some residual water molecules close to the active site.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Physical Chemistry B
ISSN
1520-6106
e-ISSN
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Volume of the periodical
121
Issue of the periodical within the volume
29
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
7027-7041
UT code for WoS article
000406726700005
EID of the result in the Scopus database
2-s2.0-85026553265