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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Frustration, specific sequence dependence, and nonlinearity in large-amplitude fluctuations of allosteric proteins
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Frustration, specific sequence dependence, and nonlinearity in large-amplitude fluctuations of allosteric proteins

机译：变构蛋白大幅度波动中的挫败感，特定序列依赖性和非线性

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摘要

Proteins have often evolved sequences so as to acquire the ability for regulation via allosteric conformational change. Here we investigate how allosteric dynamics is designed through sequences with nonlinear interaction features. First, for 71 allosteric proteins of which two, open and closed, structures are available, a statistical survey of interactions using an all-atom model with effective sol-vation shows that those residue contact interactions specific to one of the two states are significantly weaker than are the contact interactions shared by the two states. This interaction feature indicates there is underlying sequence design to facilitate conformational change. Second, based on the energy landscape theory, we implement these interaction features into a new atomic-interaction-based coarse-grained model via a multiscale simulation protocol (AICG). The AICG model outperforms standard coarse-grained models for predictions of the native-state mean fluctuations and of the conformational change direction. Third, using the new model for adenylate kinase, we show that intrinsic fluctuations in one state contain rare and large-amplitude motions nearly reaching the other state. Such large-amplitude motions are realized partly by sequence specificity and partly by the nonlinear nature of contact interactions, leading to cracking. Both features enhance conformational transition rates.
机译：蛋白质经常进化出序列，以便通过变构构象变化获得调节能力。在这里，我们研究如何通过具有非线性相互作用特征的序列设计变构动力学。首先，对于71种变构蛋白，其中两种结构具有开放和封闭结构，使用有效溶解的全原子模型对相互作用的统计调查表明，特定于两种状态之一的那些残基接触相互作用明显较弱比这两个国家共享的联系互动。该相互作用特征表明存在潜在的序列设计以促进构象改变。其次，基于能量景观理论，我们通过多尺度模拟协议（AICG）将这些相互作用特征实现到基于原子相互作用的新粗粒度模型中。 AICG模型在预测原始状态平均波动和构象变化方向方面优于标准的粗粒度模型。第三，使用腺苷酸激酶的新模型，我们显示了一种状态的内在波动包含几乎到达另一种状态的稀有大振幅运动。这样的大振幅运动部分通过序列特异性实现，部分通过接触相互作用的非线性性质实现，从而导致破裂。两种功能均可提高构象转化率。

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  • 作者

    Wenfei Li; Peter G. Wolynes; Shoji Takada;

  • 作者单位

    Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan Department of Physics, Nanjing University, Nanjing 210093, China;

    Department of Chemistry and Biochemistry and the Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093;

    Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    multiscale simulations; energy decomposition; allosteric motions; sequence design principle; interaction nonlinearity;

    机译：多尺度模拟;能量分解变构动作;顺序设计原理;相互作用非线性;

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