Automated Training of ReaxFF Reactive Force Fields for Energetics of Enzymatic Reactions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00102246" target="_blank" >RIV/00216224:14740/18:00102246 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.jctc.7b00870" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.7b00870</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.7b00870" target="_blank" >10.1021/acs.jctc.7b00870</a>
Alternative languages
Result language
angličtina
Original language name
Automated Training of ReaxFF Reactive Force Fields for Energetics of Enzymatic Reactions
Original language description
Computational studies of the reaction mechanisms of various enzymes are nowadays based almost exclusively on hybrid QM/MM models. Unfortunately, the success of this approach strongly depends on the selection of the QM region, and computational cost is a crucial limiting factor. An interesting alternative is offered by empirical reactive molecular force fields, especially the ReaxFF potential developed by van Duin and co-workers. However, even though an initial parametrization of ReaxFF for biomolecules already exists, it does not provide the desired level of accuracy. We have conducted a thorough refitting of the ReaxFF force field to improve the description of reaction energetics. To minimize the human effort required, we propose a fully automated approach to generate an extensive training set comprised of thousands of different geometries and molecular fragments starting from a few model molecules. Electrostatic parameters were optimized with QM electrostatic potentials as the main target quantity, avoiding excessive dependence on the choice of reference atomic charges and improving robustness and transferability. The remaining force field parameters were optimized using the VD-CMA-ES variant of the CMA-ES optimization algorithm. This method is able to optimize hundreds of parameters simultaneously with unprecedented speed and reliability. The resulting force field was validated on a real enzymatic system, ppGalNAcT2 glycosyltransferase. The new force field offers excellent qualitative agreement with the reference QM/MM reaction energy profile, matches the relative energies of intermediate and product minima almost exactly, and reduces the overestimation of transition state energies by 27-48% compared with the previous parametrization.
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
10610 - Biophysics
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
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 Chemical Theory and Computation
ISSN
1549-9618
e-ISSN
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Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
291-302
UT code for WoS article
000419998300026
EID of the result in the Scopus database
2-s2.0-85040347593