A STATISTICAL-MECHANICAL MODEL FOR HYDROGEN-EXCHANGE IN GLOBULAR-PROTEINS
A STATISTICAL-MECHANICAL MODEL FOR HYDROGEN-EXCHANGE IN GLOBULAR-PROTEINS
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DOI：
10.1002/pro.5560040921
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发表时间：
1995-09-01
期刊：
影响因子：
8
通讯作者：
DILL, KA
中科院分区：
文献类型：
--
作者：
MILLER, DW;DILL, KA
我们发展了球状蛋白质氢交换机制的统计力学理论。使用HP晶格模型，我们探讨了如何溶剂accesperity的链单体变化的蛋白质波动，从他们的稳定的天然构象。该模型解释了为什么在不同的蛋白质稳定性条件下，氢交换似乎涉及两种机制：（1）一种“全局展开”机制，所有质子以相似的速率交换，接近变性蛋白质的速率，以及（2）一种“稳定状态”机制，质子交换的速率可以相差许多数量级。关于稳定态机制一直存在一些争议：交换是在蛋白质内部通过溶剂渗透发生的，还是在蛋白质外部通过亚区域的局部展开发生的？本模型表明，交换的稳定状态的机制发生通过合奏的构象，其中一些可能承担非常小的相似之处，本地结构。虽然大多数波动是小幅度的运动，涉及溶剂渗透或局部展开，其他波动（构象远亲）可以涉及更大的瞬态偏移到完全不同的链折叠。
We develop a statistical mechanical theory for the mechanism of hydrogen exchange in globular proteins. Using the HP lattice model, we explore how the solvent accessibilities of chain monomers vary as proteins fluctuate from their stable native conformations. The model explains why hydrogen exchange appears to involve two mechanisms under different conditions of protein stability: (1) a ''global unfolding'' mechanism by which all protons exchange at a similar rate, approaching that of the denatured protein, and (2) a ''stable-state'' mechanism by which, protons exchange at rates that can differ by many orders of magnitude. There has been some controversy about the stable-state mechanism: does exchange take place inside the protein by solvent penetration, or outside the protein by the local unfolding of a subregion? The present model indicates that the stable-state mechanism of exchange occurs through an ensemble of conformations, some of which may bear very little resemblance to the native structure. Although most fluctuations are small-amplitude motions involving solvent penetration or local unfolding, other fluctuations (the conformational distant relatives) can involve much larger transient excursions to completely different chain folds.