Theory of single-molecule biophysics

单分子实验可以从根本上揭示关于单个生物分子的结构、动力学和相互作用的新颖和独特的信息。 单分子蛋白质折叠。蛋白质折叠通常被描述为在自由能表面上的扩散。我们建立并量化了蛋白质折叠的扩散模型(1)。这些全定量模型表明，在单分子实验分析中经常进行的近似是相当准确的，至少对于我们可以通过粗粒度分子模拟来研究的小模型蛋白质是如此。 分子尺度上的流体动力学。在溶液中，与络合物的结合和解离相关的平移运动受到所谓的流体动力相互作用的影响。我们已经为一个模型系统量化了这些流体动力学相互作用，并表明简单的流体动力学模型，如Osee张量及其改进确实捕捉到了总体影响，但在分子尺度上有显著的偏差(2)。 折叠过渡路径时间。转变路径是区分转变事件的独特的单分子性质。可以说，它们包含了所有与过渡相关的机械性信息，如蛋白质和核酸折叠。在评论跃迁路径时间分布的实验研究时，我们检查了用于研究这些重要力学事件的理论和单分子实验方法(3)。 1.R.B.Best，G.Hummer，蛋白质折叠的扩散模型，Phys.化学。化学。太棒了。13,16902-16911(2011年)。 2.J.Mittal，G.Hummer，稠密流体中的对扩散、流体动力相互作用和有效体积，J.化学。太棒了。137,034110(2012年)。 3.G.Hummer，W.A.Eaton，《观点：来自力光谱的DNA和RNA折叠的过渡路径时间》，物理5，87(2012)。

Single-molecule experiments can reveal fundamentally novel and unique information on the structure, dynamics, and interactions of individual biomolecules. Single-molecule protein folding. Protein folding is often described as diffusion on a free energy surface. We have developed and quantified diffusion models of protein folding (1). These fully quantitative models showed that the approximations frequently made in the analysis of single-molecule experiments are reasonably accurate, at least for the small model proteins we could study by coarse-grained molecular simulations. Hydrodynamics at the molecular scale. In solution, the translational motions, associated for instance with binding and dissociation of complexes, are affected by so-called hydrodynamic interactions. We have quantified these hydrodynamic interactions for a model system and showed that simple hydrodynamic models such as the Oseen tensor and their refinements indeed capture the gross effects, but with significant deviations at the molecular scale (2). Folding transition path times. Transition paths are a distinct single-molecule property that separate out transition events. Arguably, they contain all mechanistic information relevant for a transition such as protein and nucleic-acid folding. In commenting on experimental studies of transition path time distributions, we have examined the theory and single-molecule experimental approaches used to study these mechanistically important events (3). 1. R. B. Best, G. Hummer, Diffusion models of protein folding, Phys. Chem. Chem. Phys. 13, 16902-16911 (2011). 2. J. Mittal, G. Hummer, Pair diffusion, hydrodynamic interactions, and available volume in dense fluids, J. Chem. Phys. 137, 034110 (2012). 3. G. Hummer, W. A. Eaton, Viewpoint: Transition path times for DNA and RNA folding from force spectroscopy, Physics 5, 87 (2012).