Thermal unfolding of alpha-lactalbumin at acidic pH: Insights from molecular dynamics simulations

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2024-11-01 DOI:10.1016/j.jmgm.2024.108900

Elena Ermakova , Rauf Kurbanov , Igor Sedov , Yuriy Zuev

引用次数: 0

Abstract

The transformation of globular proteins into fibrils passes through several stages, including the formation of partially expanded conformational states different from the native or fully unfolded forms. Here we used molecular dynamics simulations to characterize the thermal unfolding of alpha-lactalbumin on the microsecond timescale in the range of temperatures of 300–440 K. Comparative analysis of structural changes, mobility of different parts of protein, and pathways through the free energy landscape during the unfolding of alpha-lactalbumin at different temperatures reveals the existence of several intermediate states separated by small energy barriers. The lifetime of these intermediates depends on temperature and varies from nanoseconds to microseconds.

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α-乳白蛋白在酸性 pH 条件下的热折叠：分子动力学模拟的启示。

球状蛋白质转化为纤维需要经过几个阶段，包括形成不同于原生或完全展开形式的部分展开构象状态。在这里，我们使用分子动力学模拟来描述α-乳白蛋白在 300-440 K 温度范围内的微秒级热折叠过程。通过对不同温度下α-乳白蛋白折叠过程中的结构变化、蛋白质不同部分的流动性以及自由能谱的路径进行比较分析，我们发现存在几个被小能量壁垒分隔的中间状态。这些中间状态的寿命取决于温度，从纳秒到微秒不等。

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

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.