Journal of Computational Chemistry, volume 36, issue 21, pages 1621-1630

Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling

Publication typeJournal Article
Publication date2015-07-01
Quartile SCImago
Q1
Quartile WOS
Q3
Impact factor3
ISSN01928651, 1096987X
General Chemistry
Computational Mathematics
Abstract
The mechanism of enzymatic peptide hydrolysis in matrix metalloproteinase‐2 (MMP‐2) was studied at atomic resolution through quantum mechanics/molecular mechanics (QM/MM) simulations. An all‐atom three‐dimensional molecular model was constructed on the basis of a crystal structure from the Protein Data Bank (ID: 1QIB), and the oligopeptide Ace‐Gln‐Gly∼Ile‐Ala‐Gly‐Nme was considered as the substrate. Two QM/MM software packages and several computational protocols were employed to calculate QM/MM energy profiles for a four‐step mechanism involving an initial nucleophilic attack followed by hydrogen bond rearrangement, proton transfer, and CN bond cleavage. These QM/MM calculations consistently yield rather low overall barriers for the chemical steps, in the range of 5–10 kcal/mol, for diverse QM treatments (PBE0, B3LYP, and BB1K density functionals as well as local coupled cluster treatments) and two MM force fields (CHARMM and AMBER). It, thus, seems likely that product release is the rate‐limiting step in MMP‐2 catalysis. This is supported by an exploration of various release channels through QM/MM reaction path calculations and steered molecular dynamics simulations. © 2015 Wiley Periodicals, Inc.

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Vasilevskaya T. et al. Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling // Journal of Computational Chemistry. 2015. Vol. 36. No. 21. pp. 1621-1630.
GOST all authors (up to 50) Copy
Vasilevskaya T., Khrenova M. G., Nemukhin A., Thiel W. Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling // Journal of Computational Chemistry. 2015. Vol. 36. No. 21. pp. 1621-1630.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1002/jcc.23977
UR - https://doi.org/10.1002%2Fjcc.23977
TI - Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling
T2 - Journal of Computational Chemistry
AU - Vasilevskaya, Tatiana
AU - Khrenova, Maria G.
AU - Nemukhin, Alexander
AU - Thiel, Walter
PY - 2015
DA - 2015/07/01 00:00:00
PB - Wiley
SP - 1621-1630
IS - 21
VL - 36
SN - 0192-8651
SN - 1096-987X
ER -
BibTex |
Cite this
BibTex Copy
@article{2015_Vasilevskaya
author = {Tatiana Vasilevskaya and Maria G. Khrenova and Alexander Nemukhin and Walter Thiel},
title = {Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling},
journal = {Journal of Computational Chemistry},
year = {2015},
volume = {36},
publisher = {Wiley},
month = {jul},
url = {https://doi.org/10.1002%2Fjcc.23977},
number = {21},
pages = {1621--1630},
doi = {10.1002/jcc.23977}
}
MLA
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MLA Copy
Vasilevskaya, Tatiana, et al. “Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling.” Journal of Computational Chemistry, vol. 36, no. 21, Jul. 2015, pp. 1621-1630. https://doi.org/10.1002%2Fjcc.23977.
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