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Int. J. Mol. Sci. 2016, 17(8), 1372; doi:10.3390/ijms17081372

How Many Conformations of Enzymes Should Be Sampled for DFT/MM Calculations? A Case Study of Fluoroacetate Dehalogenase

1
Environment Research Institute, Shandong University, Jinan 250100, China
2
Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.
*
Author to whom correspondence should be addressed.
Academic Editor: Henry Chermette
Received: 21 July 2016 / Revised: 12 August 2016 / Accepted: 16 August 2016 / Published: 20 August 2016
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Abstract

The quantum mechanics/molecular mechanics (QM/MM) method (e.g., density functional theory (DFT)/MM) is important in elucidating enzymatic mechanisms. It is indispensable to study “multiple” conformations of enzymes to get unbiased energetic and structural results. One challenging problem, however, is to determine the minimum number of conformations for DFT/MM calculations. Here, we propose two convergence criteria, namely the Boltzmann-weighted average barrier and the disproportionate effect, to tentatively address this issue. The criteria were tested by defluorination reaction catalyzed by fluoroacetate dehalogenase. The results suggest that at least 20 conformations of enzymatic residues are required for convergence using DFT/MM calculations. We also tested the correlation of energy barriers between small QM regions and big QM regions. A roughly positive correlation was found. This kind of correlation has not been reported in the literature. The correlation inspires us to propose a protocol for more efficient sampling. This saves 50% of the computational cost in our current case. View Full-Text
Keywords: quantum mechanics/molecular mechanics; enzymatic dehalogenation; Boltzmann-weighted average barrier; disproportionate effect quantum mechanics/molecular mechanics; enzymatic dehalogenation; Boltzmann-weighted average barrier; disproportionate effect
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Li, Y.; Zhang, R.; Du, L.; Zhang, Q.; Wang, W. How Many Conformations of Enzymes Should Be Sampled for DFT/MM Calculations? A Case Study of Fluoroacetate Dehalogenase. Int. J. Mol. Sci. 2016, 17, 1372.

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