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在尿素诱导溶菌酶展开中起关键作用的关键残基。

Key residues that play a critical role in urea-induced lysozyme unfolding.

机构信息

College of Engineering, Center for Theoretical Biology, and State Key Laboratory for Turbulence and Complex Systems, Peking University, Beijing 100871, China.

出版信息

J Phys Chem B. 2010 Dec 2;114(47):15687-93. doi: 10.1021/jp1052453. Epub 2010 Nov 5.

Abstract

In this paper, we have developed a simple sensitivity score, based on the relative population of solvent molecules near each residue, to analyze the detailed motions of both urea and water around the hen egg-white lysozyme protein (W62G mutant) during its early stage of urea-induced unfolding for a better understanding of the atomic picture of the chemical denaturation process. Our simulation and analysis show that some hydrophobic core residues can keep dry from water for tens of nanoseconds in 8 M urea, while their contacts with urea increase significantly at the same time, forming a molten dry-globule-like state. Also, different from previously proposed actions that urea molecules preferentially absorb onto charged residues, our analysis shows that the noncharged residues, rather than the charged ones, attract more urea molecules in their surroundings (acting as attractants for urea), which is consistent with our earlier findings that urea molecules preferentially bind to protein through their stronger dispersion interactions than water. Once the initial adsorption surrounding the protein surface is accomplished, the further intrusion is found to be facilitated by a group of key residues, including Leu8, Met12, Val29, and Ala95, which play a critical role in the formation of the dry-globule structure. These hydrophobic dry residues form a local contact map which excludes the intrusion of water but accommodates the presence of urea due to their stronger binding to protein during this swelling process, thus maintaining an interesting transient dry-globule state.

摘要

在本文中,我们开发了一种简单的敏感性评分,基于溶剂分子在每个残基附近的相对分布,来分析在脲诱导的鸡卵清溶菌酶蛋白(W62G 突变体)早期展开过程中脲和水围绕蛋白质的详细运动,以便更好地理解化学变性过程的原子图像。我们的模拟和分析表明,在 8 M 脲中,一些疏水核心残基可以保持数十纳秒的干燥状态而不与水接触,而同时它们与脲的接触显著增加,形成一种熔融的干燥球样状态。此外,与之前提出的脲分子优先吸附在带电荷残基上的观点不同,我们的分析表明,非带电残基而不是带电残基在其周围吸引更多的脲分子(作为脲的吸引剂),这与我们之前的发现一致,即脲分子通过与蛋白质的更强的色散相互作用而优先与蛋白质结合,而不是与水结合。一旦完成了蛋白质表面的初始吸附,就会发现进一步的侵入是由一组关键残基(包括 Leu8、Met12、Val29 和 Ala95)促进的,它们在形成干燥球结构中起着关键作用。这些疏水性干燥残基形成一个局部接触图,由于在这个肿胀过程中它们与蛋白质的结合更强,因此排除了水的侵入,但容纳了脲的存在,从而保持了一种有趣的瞬态干燥球状态。

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