On the free energy of protein folding in optical tweezers experiments.

IF 4.9 Q1 BIOPHYSICS
Biophysical reviews Pub Date : 2025-04-22 eCollection Date: 2025-04-01 DOI:10.1007/s12551-025-01310-0
Christian A M Wilson, Camila G Corrêa
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引用次数: 0

Abstract

Free energy is a critical parameter in understanding the equilibrium in chemical reactions. It enables us to determine the equilibrium proportion between the different species in the reaction and to predict in which direction the reaction will proceed if a change is performed in the system. Historically, to calculate this value, bulk experiments were performed where a parameter was altered at a gradual rate to change the population until a new equilibrium was established. In protein folding studies, it is common to vary the temperature or chaotropic agents in order to change the population and then to extrapolate to physiological conditions. Such experiments were time-consuming due to the necessity of ensuring equilibrium and reversibility. Techniques of single-molecule manipulation, such as optical/magnetic tweezers and atomic force microscopy, permit the direct measurement of the work performed by a protein undergoing unfolding/refolding at particular forces. Also, with the development of non-equilibrium free energy theorems (Jarzynski equality, Crooks fluctuation theorem, Bennett acceptance ratio, and overlapping method), it is possible to obtain free energy values in experiments far from equilibrium. This review compares different methodologies and their application in optical tweezers. Interestingly, in many proteins, discrepancies in free energy values obtained through different methods suggest additional complexities in the folding pathway, possibly involving intermediate states such as the molten globule. Further studies are needed to confirm their presence and significance.

Supplementary information: The online version contains supplementary material available at 10.1007/s12551-025-01310-0.

光镊实验中蛋白质折叠自由能的研究。
自由能是理解化学反应平衡的一个关键参数。它使我们能够确定反应中不同物质之间的平衡比例,并预测如果系统发生变化,反应将朝哪个方向进行。从历史上看,为了计算这个值,进行了大量实验,其中以渐进的速率改变参数以改变种群,直到建立新的平衡。在蛋白质折叠研究中,通常通过改变温度或混沌剂来改变种群,然后推断生理条件。由于必须保证平衡和可逆性,这种实验是费时的。单分子操作技术,如光学/磁镊子和原子力显微镜,可以直接测量蛋白质在特定力下展开/再折叠所做的功。此外,随着非平衡态自由能定理(Jarzynski等式、Crooks涨落定理、Bennett接受比、重叠法)的发展,在远离平衡态的实验中获得自由能值成为可能。本文比较了不同的方法及其在光镊中的应用。有趣的是,在许多蛋白质中,通过不同方法获得的自由能值的差异表明折叠途径中存在额外的复杂性,可能涉及中间状态,如熔融球。需要进一步的研究来证实它们的存在和意义。补充信息:在线版本包含补充资料,提供地址为10.1007/s12551-025-01310-0。
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
Biophysical reviews
Biophysical reviews Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
8.90
自引率
0.00%
发文量
93
期刊介绍: Biophysical Reviews aims to publish critical and timely reviews from key figures in the field of biophysics. The bulk of the reviews that are currently published are from invited authors, but the journal is also open for non-solicited reviews. Interested authors are encouraged to discuss the possibility of contributing a review with the Editor-in-Chief prior to submission. Through publishing reviews on biophysics, the editors of the journal hope to illustrate the great power and potential of physical techniques in the biological sciences, they aim to stimulate the discussion and promote further research and would like to educate and enthuse basic researcher scientists and students of biophysics. Biophysical Reviews covers the entire field of biophysics, generally defined as the science of describing and defining biological phenomenon using the concepts and the techniques of physics. This includes but is not limited by such areas as: - Bioinformatics - Biophysical methods and instrumentation - Medical biophysics - Biosystems - Cell biophysics and organization - Macromolecules: dynamics, structures and interactions - Single molecule biophysics - Membrane biophysics, channels and transportation
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