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

Vasilevskaya T., Khrenova M.G., Nemukhin A.V., Thiel W.
Тип документаJournal Article
Дата публикации2016-07-15
Название журналаJournal of computational chemistry
  • General Chemistry
  • Computational Mathematics
Краткое описание
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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1. Vasilevskaya T. и др. Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2 // Journal of Computational Chemistry. 2016. Т. 37. № 19. С. 1801–1809.


DO - 10.1002/jcc.24395

UR -

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 V.

AU - Thiel, Walter

PY - 2016

DA - 2016/05/03

PB - Wiley

SP - 1801-1809

IS - 19

VL - 37

SN - 0192-8651

ER -

BibTex |


doi = {10.1002/jcc.24395},

url = {},

year = 2016,

month = {may},

publisher = {Wiley},

volume = {37},

number = {19},

pages = {1801--1809},

author = {Tatiana Vasilevskaya and Maria G. Khrenova and Alexander V. Nemukhin and Walter Thiel},

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


Vasilevskaya, Tatiana et al. “Methodological Aspects of QM/MM Calculations: A Case Study on Matrix Metalloproteinase-2.” Journal of Computational Chemistry 37.19 (2016): 1801–1809. Crossref. Web.