Simulations of allosteric transitions
Simulations of allosteric transitions
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DOI：
10.1016/j.sbi.2011.01.012
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发表时间：
2011-04-01
影响因子：
6.8
通讯作者：
Elber, Ron
中科院分区：
文献类型：
--
作者：
Elber, Ron
变构转换是自然界用来微调蛋白质活性的微妙机制之一。效应器结合到蛋白质表面的特定位置会导致显著的活性变化，并启动构象转变，其中经常包括结构域的运动，而且是非常大的。从理论和生物物理学的角度来看，有两个问题特别耐人寻味。第一个是发射信号的传播方式，发射信号在空间上是受限的，只包括几个相互作用的原子，传播到我们经常在变构转变中看到的大规模构象转变。因此，存在一个问题，即一个微小的微扰如何被放大以产生数千个原子的运动。第二个难题是关注度、连贯性和效率。对效应器的绑定的影响有时延伸到数十埃。另一个主要的研究方向是信号如何在“嘈杂”的分子环境中传输并在如此长的距离内保持显著。在本综述中，我们考察了解决这些问题的不同理论和计算尝试。
Allosteric transitions are one of the subtler mechanisms used by nature to fine tune protein activity. Effector binding to a specific site on the protein surface induces significant activity change, and initiates a conformational transition that frequently includes domain motions and is very large. From a theoretical and biophysical perspective two problems are particularly intriguing. The first is the way in which a launching signal, which is spatially confined and includes only a few interacting atoms, is propagated to a large-scale conformational transition we frequently see in allosteric transitions. Hence, there is the question of how a small perturbation is magnified to yield motions of thousands of atoms. The second puzzle is of focus, coherence, and efficiency. The impact of the binding of the effector is sometimes extended over tens of angstroms. How the signal is transmitted and kept significant over such large distances in the 'noisy' molecular environment is another major direction of investigation. In the present review we examined different theoretical and computational attempts to solve the questions.