论文标题
PDZ3变构通信中基本步骤的非平衡建模
Nonequilibrium Modeling of the Elementary Step in PDZ3 Allosteric Communication
论文作者
论文摘要
虽然变构对蛋白质信号传导和调节至关重要，但变构通信的基本动力学过程尚不清楚。 PDZ3结构域代表了变构单域蛋白的一个主要例子，因为它具有良好的C端$α_3$ -HELIX和配体结合之间的远距离耦合。在一个有趣的实验中，Hamm及其同事采用了$α_3$ -HELIX的照片处理来启动PDZ3的构象变化，从而传播了从C末端传播到200 ns之内的界配体。进行广泛的非平衡分子动力学模拟，实验的建模再现了测得的时间尺度，并揭示了PDZ3中变构通信的详细图片。特别是，相关分析标识了连接$α_3$ -HELIX和蛋白质核心的触点网络，该网络以协同方式移动。代表一步过程并涉及直接$α_3$ - 配体联系人，该合作转变被认为是构象变化传播的基本步骤。
While allostery is of paramount importance for protein signaling and regulation, the underlying dynamical process of allosteric communication is not well understood. PDZ3 domain represents a prime example of an allosteric single-domain protein, as it features a well-established long-range coupling between the C-terminal $α_3$-helix and ligand binding. In an intriguing experiment, Hamm and coworkers employed photoswitching of the $α_3$-helix to initiate a conformational change of PDZ3 that propagates from the C-terminus to the bound ligand within 200 ns. Performing extensive nonequilibrium molecular dynamics simulations, the modeling of the experiment reproduces the measured timescales and reveals a detailed picture of the allosteric communication in PDZ3. In particular, a correlation analysis identifies a network of contacts connecting the $α_3$-helix and the core of the protein, which move in a concerted manner. Representing a one-step process and involving direct $α_3$-ligand contacts, this cooperative transition is considered as elementary step in the propagation of conformational change.
