腺苷酸激酶催化循环后期Mg<sup>2+</sup>转移的分子动力学模拟

引用本文: 崔大超, 任卫同, 李文飞, 王炜. 腺苷酸激酶催化循环后期Mg²⁺转移的分子动力学模拟[J]. 物理化学学报, 2016, 32(2): 429-435. doi: 10.3866/PKU.WHXB201511201 shu

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

腺苷酸激酶催化循环后期Mg²⁺转移的分子动力学模拟

1.
南京大学物理学院, 南京微结构国家实验室, 人工微结构科学与技术协同创新中心, 南京 210093

通讯作者: 李文飞, 王炜; 李文飞, 王炜

基金项目:
国家自然科学基金(11334004,81421091)资助项目 (11334004,81421091)

摘要: 腺苷酸激酶是一个包含三个结构域(LID 结构域、NMP结构域和CORE结构域)的蛋白质分子,其主要作用是催化化学反应Mg²⁺ + ATP + AMP ⇌ 2ADP + Mg²⁺,进而将细胞内ATP分子的浓度维持在合适的范围内。在腺苷酸激酶催化上述化学反应的过程中,需要有Mg²⁺的参与。最近的实验发现Mg²⁺不仅参与上述反应的化学步骤,而且对化学反应发生后底物的释放过程至关重要。已有晶体结构数据显示,在催化循环过程的化学反应步骤完成后,一个Mg²⁺可同时和分别位于LID 结构域及NMP结构域的两个ADP分子配位。然而,在底物的释放与分离过程中,Mg²⁺可能只与其中一个ADP分子结合。由于Mg²⁺与ADP分子的结合情况会在很大程度上影响作为催化循环限速步骤的底物释放过程,因此人们有必要研究清楚在底物释放前Mg²⁺与催化产物ADP分子的配位情况,即Mg²⁺更倾向于与LID 结构域的ADP分子结合还是与NMP结构域的ADP分子结合。本文中,我们对催化反应后底物释放前的酶-底物复合物(包含酶、两个ADP分子以及Mg²⁺)做了分子动力学模拟研究。我们基于metadynamics方法得到了Mg²⁺在两个ADP分子间转移的自由能面,发现在底物分离与释放过程中,Mg²⁺更倾向于与LID 结构域的ADP分子结合。只有当LID 结构域的ADP分子被质子化,同时NMP结构域的ADP分子处于去质子化状态时,Mg²⁺才会倾向于与NMP结构域的ADP分子结合。另外,我们也刻画了Mg²⁺转移过程中配体交换与脱水过程。本工作的研究结果有助于理解腺苷酸激酶催化循环后期的分子过程。

关键词:

English

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: 李文飞, 王炜; 李文飞, 王炜

Received Date: 28 July 2015
Fund Project:
国家自然科学基金(11334004,81421091)资助项目

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:

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

腺苷酸激酶催化循环后期Mg²⁺转移的分子动力学模拟

通讯作者: 李文飞, 王炜; 李文飞, 王炜

English

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

Corresponding author: 李文飞, 王炜; 李文飞, 王炜

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

腺苷酸激酶催化循环后期Mg2+转移的分子动力学模拟

通讯作者: 李文飞, 王炜; 李文飞, 王炜

English

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

Corresponding author: 李文飞, 王炜; 李文飞, 王炜

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

腺苷酸激酶催化循环后期Mg²⁺转移的分子动力学模拟

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

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs