title: How Many Conformations of Enzymes Should Be Sampled for DFT/MM Calculations? A Case Study of Fluoroacetate Dehalogenase.
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.
authors.affiliation: Environment Research Institute, Shandong University, Jinan 250100, China. lyw@sdu.edu.cn.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Environment Research Institute, Shandong University, Jinan 250100, China. zrm0118@163.com.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.. dulikai@mail.hzau.edu.cn.
authors.forename: Likai
authors.initials: L
authors.lastname: Du
authors.affiliation: Environment Research Institute, Shandong University, Jinan 250100, China. zqz@sdu.edu.cn.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Environment Research Institute, Shandong University, Jinan 250100, China. wxwang@sdu.edu.cn.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Wang
mesh_terms: D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D006867:Hydrolases; C023098:haloacetate dehalogenase
keywords: Boltzmann-weighted average barrier; disproportionate effect; enzymatic dehalogenation; quantum mechanics/molecular mechanics