Journal of Computational Chemistry, volume 37, issue 19, pages 1801-1809

Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2

Publication typeJournal Article
Publication date2016-05-03
Quartile SCImago
Q1
Quartile WOS
Q3
Impact factor3
ISSN01928651, 1096987X
General Chemistry
Computational Mathematics
Abstract
We address methodological issues in quantum mechanics/molecular mechanics (QM/MM) calculations on a zinc‐dependent enzyme. We focus on the first stage of peptide bond cleavage by matrix metalloproteinase‐2 (MMP‐2), that is, the nucleophilic attack of the zinc‐coordinating water molecule on the carbonyl carbon atom of the scissile fragment of the substrate. This step is accompanied by significant charge redistribution around the zinc cation, bond cleavage, and bond formation. We vary the size and initial geometry of the model system as well as the computational protocol to demonstrate the influence of these choices on the results obtained. We present QM/MM potential energy profiles for a set of snapshots randomly selected from QM/MM‐based molecular dynamics simulations and analyze the differences in the computed profiles in structural terms. Since the substrate in MMP‐2 is located on the protein surface, we investigate the influence of the thickness of the water layer around the enzyme on the QM/MM energy profile. Thin water layers (0–2 Å) give unrealistic results because of structural reorganizations in the active‐site region at the protein surface. A 12 Å water layer appears to be sufficient to capture the effect of the solvent; the corresponding QM/MM energy profile is very close to that obtained from QM/MM/SMBP calculations using the solvent macromolecular boundary potential (SMBP). We apply the optimized computational protocol to explain the origin of the different catalytic activity of the Glu116Asp mutant: the energy barrier for the first step is higher, which is rationalized on structural grounds. © 2016 Wiley Periodicals, Inc.

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Vasilevskaya T. et al. Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2 // Journal of Computational Chemistry. 2016. Vol. 37. No. 19. pp. 1801-1809.
GOST all authors (up to 50) Copy
Vasilevskaya T., Khrenova M. G., Nemukhin A., Thiel W. Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2 // Journal of Computational Chemistry. 2016. Vol. 37. No. 19. pp. 1801-1809.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1002/jcc.24395
UR - https://doi.org/10.1002%2Fjcc.24395
TI - Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2
T2 - Journal of Computational Chemistry
AU - Vasilevskaya, Tatiana
AU - Khrenova, Maria G.
AU - Nemukhin, Alexander
AU - Thiel, Walter
PY - 2016
DA - 2016/05/03 00:00:00
PB - Wiley
SP - 1801-1809
IS - 19
VL - 37
SN - 0192-8651
SN - 1096-987X
ER -
BibTex |
Cite this
BibTex Copy
@article{2016_Vasilevskaya
author = {Tatiana Vasilevskaya and Maria G. Khrenova and Alexander Nemukhin and Walter Thiel},
title = {Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2},
journal = {Journal of Computational Chemistry},
year = {2016},
volume = {37},
publisher = {Wiley},
month = {may},
url = {https://doi.org/10.1002%2Fjcc.24395},
number = {19},
pages = {1801--1809},
doi = {10.1002/jcc.24395}
}
MLA
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Vasilevskaya, Tatiana, et al. “Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2.” Journal of Computational Chemistry, vol. 37, no. 19, May. 2016, pp. 1801-1809. https://doi.org/10.1002%2Fjcc.24395.
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