噬菌体MS2的变构转换机制
The Allosteric Switching Mechanism in Bacteriophage MS2
摘要：
在这篇文章中，我们使用全原子模拟来阐明的机制，潜在的构象转换和变构内的外壳蛋白的噬菌体MS2。大多数二十面体病毒衣壳的组装需要衣壳蛋白在衣壳内的精确位置处采用不同的构象。已经表明，来自MS2基因组的19个核苷酸的茎环（TR）充当变构效应物，在衣壳组装期间引导外壳蛋白的构象转换。由于主要的构象变化发生在远离TR结合位点的地方，因此了解这种变构通讯的分子机制是很重要的。为此，我们使用全原子模拟与明确的水结合的路径采样技术来采样的MS2外壳蛋白的构象转变，在TR结合的存在和不存在。计算发现，TR绑定强烈改变的过渡自由能分布，导致开关的青睐的构象。我们讨论了负责这种转变的分子相互作用的变化。然后，我们确定网络的氨基酸与相关的议案，揭示了TR绑定的影响跨越蛋白质的机制。分析预测氨基酸的突变取代可能会改变人口的构象substates或其转换速率。
英文摘要：
In this article we use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopt different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.
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