The use of force probes to induce unfolding and refolding of single molecules through the application of mechanical tension, known as single-molecule force spectroscopy (SMFS), has proven to be a powerful tool for studying the dynamics of protein folding. Here we provide an overview of what has been learned about protein folding using SMFS, from small, single-domain proteins to large, multi-domain proteins. We highlight the ability of SMFS to measure the energy landscapes underlying folding, to map complex pathways for native and non-native folding, to probe the mechanisms of chaperones that assist with native folding, to elucidate the effects of the ribosome on co-translational folding, and to monitor the folding of membrane proteins.

使用力探针通过施加机械张力来诱导单分子的展开和重新折叠，称为单分子力谱 (SMFS)，已被证明是研究蛋白质折叠动力学的有力工具。在这里，我们概述了关于使用 SMFS 进行蛋白质折叠的知识，从小的单域蛋白质到大的多域蛋白质。我们强调了 SMFS 测量折叠潜在能量景观的能力，绘制天然和非天然折叠的复杂途径，探索辅助天然折叠的分子伴侣的机制，阐明核糖体对共翻译折叠的影响，并监测膜蛋白的折叠。