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Explicit Solvation Matters: Performance of QM/MM Solvation Models in Nucleophilic Addition
[Image: see text] Nucleophilic addition onto a carbonyl moiety is strongly affected by solvent, and correctly simulating this solvent effect is often beyond the capability of single-scale quantum mechanical (QM) models. This work explores multiscale approaches for the description of the reversible a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023263/ https://www.ncbi.nlm.nih.gov/pubmed/29438621 http://dx.doi.org/10.1021/acs.jctc.7b01206 |
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author | Boereboom, Jelle M. Fleurat-Lessard, Paul Bulo, Rosa E. |
author_facet | Boereboom, Jelle M. Fleurat-Lessard, Paul Bulo, Rosa E. |
author_sort | Boereboom, Jelle M. |
collection | PubMed |
description | [Image: see text] Nucleophilic addition onto a carbonyl moiety is strongly affected by solvent, and correctly simulating this solvent effect is often beyond the capability of single-scale quantum mechanical (QM) models. This work explores multiscale approaches for the description of the reversible and highly solvent-sensitive nucleophilic N|···C=O bond formation in an Me(2)N–(CH(2))(3)–CH=O molecule. In the first stage of this work, we rigorously compare and test four recent quantum mechanical/molecular mechanical (QM/MM) explicit solvation models, employing a QM description of water molecules in spherical regions around both the oxygen and the nitrogen atom of the solute. The accuracy of the models is benchmarked against a reference QM simulation, focusing on properties of the solvated Me(2)N–(CH(2))(3)–CH=O molecule in its ring-closed form. In the second stage, we select one of the models (continuous adaptive QM/MM) and use it to obtain a reliable free energy profile for the N|···C bond formation reaction. We find that the dual-sphere approach allows the model to accurately account for solvent reorganization along the entire reaction path. In contrast, a simple microsolvation model cannot adapt to the changing conditions and provides an incorrect description of the reaction process. |
format | Online Article Text |
id | pubmed-6023263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-60232632018-06-29 Explicit Solvation Matters: Performance of QM/MM Solvation Models in Nucleophilic Addition Boereboom, Jelle M. Fleurat-Lessard, Paul Bulo, Rosa E. J Chem Theory Comput [Image: see text] Nucleophilic addition onto a carbonyl moiety is strongly affected by solvent, and correctly simulating this solvent effect is often beyond the capability of single-scale quantum mechanical (QM) models. This work explores multiscale approaches for the description of the reversible and highly solvent-sensitive nucleophilic N|···C=O bond formation in an Me(2)N–(CH(2))(3)–CH=O molecule. In the first stage of this work, we rigorously compare and test four recent quantum mechanical/molecular mechanical (QM/MM) explicit solvation models, employing a QM description of water molecules in spherical regions around both the oxygen and the nitrogen atom of the solute. The accuracy of the models is benchmarked against a reference QM simulation, focusing on properties of the solvated Me(2)N–(CH(2))(3)–CH=O molecule in its ring-closed form. In the second stage, we select one of the models (continuous adaptive QM/MM) and use it to obtain a reliable free energy profile for the N|···C bond formation reaction. We find that the dual-sphere approach allows the model to accurately account for solvent reorganization along the entire reaction path. In contrast, a simple microsolvation model cannot adapt to the changing conditions and provides an incorrect description of the reaction process. American Chemical Society 2018-02-13 2018-04-10 /pmc/articles/PMC6023263/ /pubmed/29438621 http://dx.doi.org/10.1021/acs.jctc.7b01206 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Boereboom, Jelle M. Fleurat-Lessard, Paul Bulo, Rosa E. Explicit Solvation Matters: Performance of QM/MM Solvation Models in Nucleophilic Addition |
title | Explicit Solvation Matters: Performance of QM/MM Solvation
Models in Nucleophilic Addition |
title_full | Explicit Solvation Matters: Performance of QM/MM Solvation
Models in Nucleophilic Addition |
title_fullStr | Explicit Solvation Matters: Performance of QM/MM Solvation
Models in Nucleophilic Addition |
title_full_unstemmed | Explicit Solvation Matters: Performance of QM/MM Solvation
Models in Nucleophilic Addition |
title_short | Explicit Solvation Matters: Performance of QM/MM Solvation
Models in Nucleophilic Addition |
title_sort | explicit solvation matters: performance of qm/mm solvation
models in nucleophilic addition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023263/ https://www.ncbi.nlm.nih.gov/pubmed/29438621 http://dx.doi.org/10.1021/acs.jctc.7b01206 |
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