Microscopic Significance of Hydrophobic Residues for Protein Stability in Ionic Liquids.

IF 2.8 2区 化学 Q3 CHEMISTRY, PHYSICAL
The Journal of Physical Chemistry B Pub Date : 2025-03-27 Epub Date: 2025-03-17 DOI:10.1021/acs.jpcb.5c00236
Guochao Sun, Bing Fang, Yanmei Yang, Yuanyuan Qu, Qingmeng Zhang, Weifeng Li
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引用次数: 0

Abstract

It is well-known that ionic liquids (ILs) can alter the structural stability of proteins. The change in protein conformation is closely related to the interaction between the protein residue and ILs. To probe the impact of hydrophobic interactions on protein stability in ILs, we conducted molecular dynamic simulations and compared the unfolding process of two proteins, the wild-type villin headpiece protein HP35 and its doubly mutant form HP35NN which contains two hydrophobic norleucine (NLE) substitutions at Lys24/29, in hydrated 1-butyl-3-methylimidazolium chloride ([BMIM]Cl). By sampling at a long time scale, the denaturation ability of ILs was well captured. Specifically, HP35NN exhibits greater structural instability than HP35, characterized by the unfolding of helix-3 where the mutated hydrophobic residues are located. These findings highlight the thermodynamic instability of the protein caused by the mutation of two hydrophobic residues in the ILs. By evaluating the hydration kinetics of helix-3 with ILs, we found that the intramolecular hydrogen bonds of HP35NN were broken. At the same time, HP35NN binds to more ILs through hydrophobic interactions. Therefore, we propose that the hydrophobic interaction between ILs and the mutated hydrophobic residue plays a crucial role in the denaturation of HP35NN. The stability comparison and verification of the alkyl chain model of hydrophobic residues in ILs also further prove the instability of hydrophobic residue mutation in ILs. These findings may provide valuable basic information for understanding the effect of ILs on the conformational stability of proteins.

疏水残基对离子液体中蛋白质稳定性的微观意义。
众所周知,离子液体可以改变蛋白质的结构稳定性。蛋白质构象的改变与蛋白质残基与il的相互作用密切相关。为了探讨疏水相互作用对ILs中蛋白质稳定性的影响,我们进行了分子动力学模拟,并比较了两种蛋白质的展开过程,野生型绒毛头蛋白HP35和其双突变型HP35NN在水合1-丁基-3-甲基咪唑氯([BMIM]Cl)中含有两个疏水去甲亮氨酸(NLE)取代的Lys24/29。通过长时间采样,很好地捕捉到了il的变性能力。具体来说,HP35NN比HP35表现出更大的结构不稳定性,其特征是突变疏水残基所在的螺旋-3展开。这些发现强调了由il中两个疏水残基突变引起的蛋白质热力学不稳定性。通过评价螺旋-3与ILs的水化动力学,我们发现HP35NN的分子内氢键被破坏。同时,HP35NN通过疏水相互作用与更多的il结合。因此,我们认为ILs与突变的疏水残基之间的疏水相互作用在HP35NN的变性中起着至关重要的作用。对ILs疏水残基烷基链模型的稳定性比较和验证也进一步证明了ILs疏水残基突变的不稳定性。这些发现可能为了解il对蛋白质构象稳定性的影响提供有价值的基础信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.80
自引率
9.10%
发文量
965
审稿时长
1.6 months
期刊介绍: An essential criterion for acceptance of research articles in the journal is that they provide new physical insight. Please refer to the New Physical Insights virtual issue on what constitutes new physical insight. Manuscripts that are essentially reporting data or applications of data are, in general, not suitable for publication in JPC B.
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