Molecular mechanism of pressure denaturation of proteins
Molecular mechanism of pressure denaturation of proteins
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DOI：
10.1063/1.2991176
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发表时间：
2008-10-14
影响因子：
4.4
通讯作者：
Kinoshita, Masahiro
中科院分区：
文献类型：
--
作者：
Harano, Yuichi;Yoshidome, Takashi;Kinoshita, Masahiro
我们利用角度相关积分方程理论结合多极水模型和形态测量方法研究了蛋白质压力变性的分子机制。我们认为蛋白质的水合熵是关键量。经证实，在升高的压力下，膨胀结构（其致密性仅比天然结构稍差，但具有更大的水可及表面积）在水熵方面变得比天然结构更稳定。膨胀结构的特点是水渗透到内部。水合熵被分解为水分子运动的平移和旋转限制的贡献。每个贡献进一步分解为水-蛋白质对相关分量和水-水-蛋白质三元组和高阶相关分量。平移贡献中的成对相关分量被分为分别由排除体积和蛋白质附近的水结构产生的两项。研究发现，压力变性伴随着成对相关水平上的平移熵和旋转熵的损失，但三重态和高阶相关水平上的平动熵的增益要大得多。尽管水分子穿透蛋白质内部并接触蛋白质表面的平移和旋转运动受到限制，但对蛋白质外部的水分子的平移限制大大减少。后者的熵增益占主导地位，导致变性。 (C) 2008 年美国物理研究所。
We investigate the molecular mechanism of pressure denaturation of proteins using the angle-dependent integral equation theory combined with the multipole water model and the morphometric approach. We argue that the hydration entropy of a protein is the key quantity. It is verified that at an elevated pressure, a swelling structure-which has only moderately less compact than the native structure but has a much larger water-accessible surface area-turns more stable than the native structure in terms of the water entropy. The swelling structure is characterized by the penetration of water into the interior. The hydration entropy is decomposed into contributions from the translational and rotational restrictions for the molecular motions of water. Each contribution is further decomposed into the water-protein pair correlation component and the water-water-protein triplet and higher-order correlation components. The pair correlation component in the translational contribution is divided into two terms arising from the excluded volume and the water structure near the protein, respectively. It is found that pressure denaturation accompanies a loss of the translational and rotational entropies at the pair correlation level but a much larger gain of the translational entropy at the triplet and higher-order correlation levels. Although the translational and rotational motions of water molecules penetrating the protein interior and contacting the protein surface are constrained, the translational restriction for the water molecules well outside the protein is greatly reduced. The latter entropic gain dominates, leading to the denaturation. (C) 2008 American Institute of Physics.