Citation: CUI Da-Chao, REN Wei-Tong, LI Wen-Fei, WANG Wei. Metadynamics Simulations of Mg²⁺ Transfer in the Late Stage of the Adenylate Kinase Catalytic Cycle[J]. Acta Physico-Chimica Sinica, ;2016, 32(2): 429-435. doi: 10.3866/PKU.WHXB201511201 shu

Metadynamics Simulations of Mg²⁺ Transfer in the Late Stage of the Adenylate Kinase Catalytic Cycle

1.
National Laboratory of Solid State Microstructure, Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China

Corresponding author: LI Wen-Fei, WANG Wei,
Received Date: 28 July 2015
Available Online: 13 November 2015
Fund Project: 国家自然科学基金(11334004,81421091)资助项目 (11334004,81421091)

Adenylate kinase is a kind of important enzymes which can catalyze the reversible reaction Mg²⁺ + ATP + AMP ⇌ 2ADP + Mg²⁺where the Mg²⁺ coordination around the active site plays a crucial role. It was shown experimentally that one Mg²⁺ ion can coordinate to both ADP molecules right after the chemical step of the catalytic reaction. During the substrate releasing and separation, the Mg²⁺ may transfer to one of the ADP molecules. However, it is unclear which ADP molecule binds with the Mg²⁺ during the substrate releasing. In this work, by using metadynamics method, we conducted molecular simulations on the adenylate kinase complexed with two ADP molecules and one Mg²⁺, which corresponds to the postcatalysis enzyme-substrate complex. We constructed the free energy landscapes characterizing the Mg²⁺ transfer to the individual ADP molecules. Our results show that the Mg²⁺ has preference to attach with the ADP molecule of the LID domain. We found that only when the LID domain ADP is protonated, and simultaneously the NMP domain ADP is deprotonated, the Mg²⁺ tends to attach with the NMP domain ADP. We also characterized the ligand exchange and dehydration processes during the Mg²⁺ transfer. Our results provide insights into the molecular process during the late state of the adenylate kinase catalytic cycle.
- Adenylate kinase,
- Mg²⁺ transfer,
- Metadynamics,
- Molecular simulation
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沈阳化工大学材料科学与工程学院沈阳 110142

Metadynamics Simulations of Mg2+ Transfer in the Late Stage of the Adenylate Kinase Catalytic Cycle

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通讯作者: 陈斌, bchen63@163.com

Metadynamics Simulations of Mg²⁺ Transfer in the Late Stage of the Adenylate Kinase Catalytic Cycle