Acta Phys. -Chim. Sin. ›› 2016, Vol. 32 ›› Issue (2): 429-435.doi: 10.3866/PKU.WHXB201511201

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

Da-Chao CUI*(),Wei-Tong REN,Wen-Fei LI,Wei WANG*()   

  • Received:2015-07-28 Published:2016-01-30
  • Contact: Da-Chao CUI,Wei WANG E-mail:wfli@nju.edu.cn;wangwei@nju.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(11334004, 81421091)

Abstract:

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.

Key words: Adenylate kinase, Mg2+ transfer, Metadynamics, Molecular simulation

MSC2000: 

  • O641