Reconstructing folding energy landscapes by single-molecule force spectroscopy.
Reconstructing folding energy landscapes by single-molecule force spectroscopy.
复制标题
DOI：
10.1146/annurev-biophys-051013-022754
复制
发表时间：
2014
影响因子：
12.4
通讯作者：
Block SM
中科院分区：
文献类型：
--
作者：
Woodside MT;Block SM
折叠在概念上可以用对应于不同分子构型的自由能景观上的轨迹来描述。在实践中，能源前景可能很难衡量。单分子力谱(SMFS)，通过监测分子在受控力作用下的结构变化，已经成为探测能量景观的强大工具。我们总结了在平衡和非平衡条件下由力谱测量重建地貌的方法。其他补充但技术要求较低的方法提供了景观关键特征的依赖于模型的表征。一旦重建，能量景观就可以用来研究关键的折叠参数，例如结构变化所需的特征转换时间，以及为景观上的运动设定时间尺度的有效扩散系数。我们还讨论了使测量和解释复杂化的问题，包括多个状态或路径的可能性以及将多个维度投影到单个坐标上的影响。
Folding may be described conceptually in terms of trajectories over a landscape of free energies corresponding to different molecular configurations. In practice, energy landscapes can be difficult to measure. Single-molecule force spectroscopy (SMFS), whereby structural changes are monitored in molecules subjected to controlled forces, has emerged as a powerful tool for probing energy landscapes. We summarize methods for reconstructing landscapes from force spectroscopy measurements under both equilibrium and nonequilibrium conditions. Other complementary, but technically less demanding, methods provide a model-dependent characterization of key features of the landscape. Once reconstructed, energy landscapes can be used to study critical folding parameters, such as the characteristic transition times required for structural changes and the effective diffusion coefficient setting the timescale for motions over the landscape. We also discuss issues that complicate measurement and interpretation, including the possibility of multiple states or pathways and the effects of projecting multiple dimensions onto a single coordinate.