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Title: Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms: Application of QM/MM methods

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Departamento de Química e Bioquímica, Faculdade de Ciências, UCIBIO, REQUIMTE, Universidade do Porto, Porto Portugal
Publication Date:
Sponsoring Org.:
USDOE Office of Nuclear Energy (NE), Fuel Cycle Technologies (NE-5)
OSTI Identifier:
1400800
Grant/Contract Number:
PT2020 UID/MULTI/04378/2013; EXCL/QEQ-COM/0394/2012; EXCL-II/QEQ-COM/0394/2012; INCENTIVO/EQB/LA0006/2014; SFRH/BD/78397/2011; SFRH/BPD/94883/2013
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Wiley Interdisciplinary Reviews: Computational Molecular Science
Additional Journal Information:
Journal Volume: 7; Journal Issue: 2; Related Information: CHORUS Timestamp: 2017-10-20 15:40:10; Journal ID: ISSN 1759-0876
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
United States
Language:
English

Citation Formats

Sousa, Sérgio Filipe, Ribeiro, António J. M., Neves, Rui P. P., Brás, Natércia F., Cerqueira, Nuno M. F. S. A., Fernandes, Pedro A., and Ramos, Maria João. Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms: Application of QM/MM methods. United States: N. p., 2016. Web. doi:10.1002/wcms.1281.
Sousa, Sérgio Filipe, Ribeiro, António J. M., Neves, Rui P. P., Brás, Natércia F., Cerqueira, Nuno M. F. S. A., Fernandes, Pedro A., & Ramos, Maria João. Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms: Application of QM/MM methods. United States. doi:10.1002/wcms.1281.
Sousa, Sérgio Filipe, Ribeiro, António J. M., Neves, Rui P. P., Brás, Natércia F., Cerqueira, Nuno M. F. S. A., Fernandes, Pedro A., and Ramos, Maria João. 2016. "Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms: Application of QM/MM methods". United States. doi:10.1002/wcms.1281.
@article{osti_1400800,
title = {Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms: Application of QM/MM methods},
author = {Sousa, Sérgio Filipe and Ribeiro, António J. M. and Neves, Rui P. P. and Brás, Natércia F. and Cerqueira, Nuno M. F. S. A. and Fernandes, Pedro A. and Ramos, Maria João},
abstractNote = {},
doi = {10.1002/wcms.1281},
journal = {Wiley Interdisciplinary Reviews: Computational Molecular Science},
number = 2,
volume = 7,
place = {United States},
year = 2016,
month = 9
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1002/wcms.1281

Citation Metrics:
Cited by: 3works
Citation information provided by
Web of Science

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  • The CH{sub 3}Cl + CN{sup −} reaction in water was studied using a multilevel quantum mechanics/molecular mechanics (MM) method with the multilevels, electrostatic potential, density functional theory (DFT) and coupled-cluster single double triple (CCSD(T)), for the solute region. The detailed, back-side attack S{sub N}2 reaction mechanism was mapped along the reaction pathway. The potentials of mean force were calculated under both the DFT and CCSD(T) levels for the reaction region. The CCSD(T)/MM level of theory presents a free energy activation barrier height at 20.3 kcal/mol, which agrees very well with the experiment value at 21.6 kcal/mol. The results show thatmore » the aqueous solution has a dominant role in shaping the potential of mean force. The solvation effect and the polarization effect together increase the activation barrier height by ∼11.4 kcal/mol: the solvation effect plays a major role by providing about 75% of the contribution, while polarization effect only contributes 25% to the activation barrier height. Our calculated potential of mean force under the CCSD(T)/MM also has a good agreement with the one estimated using data from previous gas-phase studies.« less
  • The bimolecular nucleophilic substitution reaction of CCl{sub 4} and OH{sup -} in aqueous solution was investigated on the basis of a combined quantum mechanical and molecular mechanics method. A multilayered representation approach is employed to achieve high accuracy results at the CCSD(T) level of theory. The potential of mean force calculations at the DFT level and CCSD(T) level of theory yield reaction barrier heights of 22.7 and 27.9 kcal/mol, respectively. Both the solvation effects and the solvent-induced polarization effect have significant contributions to the reaction energetics, for example, the solvation effect raises the saddle point by 10.6 kcal/mol. The calculatedmore » rate constant coefficient is 8.6 x 10{sup -28} cm{sup 3} molecule{sup -1} s{sup -1} at the standard state condition, which is about 17 orders magnitude smaller than that in the gas phase. Among the four chloromethanes (CH{sub 3}Cl, CH{sub 2}Cl{sub 2}, CHCl{sub 3}, and CCl{sub 4}), CCl{sub 4} has the lowest free energy activation barrier for the reaction with OH{sup -1} in aqueous solution, confirming the trend that substitution of Cl by H in chloromethanes diminishes the reactivity.« less
  • The CH 2Cl 2 + OH - reaction in aqueous solution was investigated using combined quantum mechanical and molecular mechanics approach. We present analysis of the reactant, transition, and product state structures, and calculate the free energy reaction profile through the CCSD(T) level of the theory for the reactive region. Our results show that the aqueous environment has a significant impact on the reaction process raising the reaction barrier by ~17 kcal/mol and the reaction energy by ~20 kcal/mol. While solvation effects play a predominant role, we also find sizable contributions from solvent-induced polarization effects.
  • The SN2 mechanism for the reaction of CH3Cl + OH- in aqueous solution was investigated using combined quantum mechanical and molecular mechanics methodology. We analyzed structures of reactant, transition and product states along the reaction pathway. The free energy profile was calculated using the multi-layered representation with the DFT and CCSD(T) level of theory for the quantum-mechanical description of the reactive region. Our results show that the aqueous environment has a significant impact on the reaction process. We find that solvation energy contribution raises the reaction barrier by ~18.9 kcal/mol and the reaction free energy by ~24.5 kcal/mol. The presencemore » of the solvent also induces perturbations in the electronic structure of the solute leading to an increase of 3.5 kcal/mol for the reaction barrier and a decrease of 5.6 kcal/mol for the reaction free energy respectively. Combining the results of two previous calculation results on CHCl3 + OH- and CH2Cl2 + OH- reactions in water, we demonstrate that increase in the chlorination of the methyl group (from CH3Cl to CHCl3) is accompanied by the decrease in the free energy reaction barrier, with the CH3Cl + OH- having the largest barrier among the three reactions.« less
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