Exploring the Thermodynamic Landscape, Kinetics, and Structural Evolution of a Protein Conformational Transition with a Microscopic Double-Well Model
Exploring the Thermodynamic Landscape, Kinetics, and Structural Evolution of a Protein Conformational Transition with a Microscopic Double-Well Model
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DOI：
10.1021/jp110845u
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发表时间：
2011-04-14
影响因子：
3.3
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Lai, Zai-Zhi;Lu, Qiang;Wang, Jin
谷氨酰胺结合蛋白(GlnBP)的功能构象转换是谷氨酰胺结合和转运的关键。在这里，我们发展了一个基于结构的双势垒模型来研究GlnBP构象转变的热力学和动力学性质。我们揭示了不同温度下构象转变的基本自由能图景。分析表明，在熔融温度以下，出现了两个吸引点盆地，分别对应于蛋白质的开放状态和关闭状态。通过首次通过时间的均值和分布以及自相关函数，研究了构象转换的动力学性质。这种动力学意味着潜在能源格局的复杂性和层级结构。我们建立了结构的接触图，以探索构象转变的结构演化。最后，计算残基的PHI值以确定过渡态的重要残基(热点)。
Functional conformational transition in the glutamine-binding protein (GlnBP) is known to be the key to bind and transfer ligand glutamine. Here, we developed a structure-based double-well model to investigate the thermodynamic and kinetic natures of the GlnBP conformational transition. We uncovered the underlying free-energy landscape of the conformational transition with different temperatures. The analysis shows that below the melting temperature, two basins of attractions emerge, corresponding to the open state and the closed state of the protein. We explored the kinetic property of the conformational switch through the mean and distribution of the first passage time as well as the autocorrelation function. The kinetics implies the complexity and the hierarchical structure of the underlying energy landscape. We built the contact maps of the structures to probe the structural evolution of the conformational transition. Finally, the phi values of the residues were calculated to identify the important residues (hot spots) of the transition state.