Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusion
Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusion
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DOI：
10.1016/j.jmb.2005.05.043
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发表时间：
2005-08-12
影响因子：
5.6
通讯作者：
Agard, DA
中科院分区：
文献类型：
--
作者：
Ota, N;Agard, DA
各种实验证据表明，通过蛋白质核心的快速、长距离的构象变化传播在变构通信中起着至关重要的作用。在这里，我们描述了一种非平衡分子动力学模拟方法，即各向异性热扩散（ATD），这使我们能够观察到PDZ结构域蛋白家族成员PSD-95的分子内显性信号通路，所观察到的途径与之前通过276个PDZ结构域蛋白的多序列分析推断的途径非常一致。与传统的溶液分子动力学方法相比，ATD方法大大增强了信噪比，可以清晰地观察到远距离相关性。ATD方法既不需要大量的同源蛋白，也不需要非常长的模拟时间来获得蛋白质内部完整的信号通路。因此，ATD方法应该被证明是对理解分子内信号传导物理基础的实验努力的有力和普遍的补充。(c) 2005 Elsevier Ltd版权所有。
A variety of experimental evidence suggests that rapid, long-range propagation of conformational changes through the core of proteins plays a vital role in allosteric communication. Here, we describe a non-equilibrium molecular dynamics simulation method, anisotropic thermal diffusion (ATD), which allowed us to observe a dominant intramolecular signaling pathway in PSD-95, a member of the PDZ domain protein family The observed pathway is in good accordance with a pathway previously inferred using a multiple sequence analysis of 276 PDZ domain proteins. In comparison with conventional solution molecular dynamics methods, the ATD method provides greatly enhanced signal-to-noise, allowing long-distance correlations to be observed clearly. The ATD method requires neither a large number of homologous proteins, nor extremely long simulation times to obtain a complete signaling pathway within a protein. Therefore, the ATD method should prove to be a powerful and general complement to experimental efforts to understand the physical basis of intramolecular signaling. (c) 2005 Elsevier Ltd. All rights reserved.