Theory of single-molecule biophysics

在单分子实验中，力可以直接施加在单个分子上，它们的响应可以作为时间的函数来跟踪。这些实验揭示了关于单个生物分子的结构、动力学和相互作用的基本新颖和独特的信息。 单分子力谱理论。在与Szabo博士(NIDDK，NIH)的合作下，我们继续发展形式主义，从单分子力谱实验中提取准确的动力学和热力学信息。在这样的分子拉力实验中，人们可以借助雅金斯基恒等式将测得的力-伸展曲线转换为整个系统的亥姆霍兹自由能。我们可以展示如何将这些自由能转化为潜在的分子自由能表面，也就是感兴趣的量。目前正在审查这项工作产生的一份文件。 受控的分子动力学。我们开发了一种用于探索低维自由能景观的反向积分方法(Frewen等人，J.Chem。太棒了。2010)。我们表明，粗略的反向积分能够有效地在地形上导航：从局部有效势井中逃脱，检测鞍点，并识别井之间的重要过渡路径。虽然最初是为了模拟而推导出来的，但单分子操纵设备，特别是光学镊子，使得在实验中使用相同的方法成为可能。

In single-molecule experiments forces can be exerted directly on individual molecules and their response can be followed as a function of time. These experiments reveal fundamentally novel and unique information on the structure, dynamics, and interactions of individual biomolecules. Theory of single molecule force spectroscopy. In collaboration with Dr. Szabo (NIDDK, NIH), we have continued our development of formalisms to extract accurate kinetic and thermodynamic information from single-molecule force spectroscopy experiments. In such molecular pulling experiments, one can transform the measured force-extension curves into Helmholtz free energies of the entire system with the help of the Jarzynski identity. We could show how these free energies can be transformed into the underlying molecular free energy surface, which is the quantity of interest. A paper resulting from this work is currently under review. Controlled molecular dynamics. We developed a reverse integration approach for the exploration of low-dimensional free energy landscapes (Frewen et al., J. Chem. Phys. 2010). We show that coarse reverse integration enables efficient navigation on the landscape terrain: Escape from local effective potential wells, detection of saddle points, and identification of significant transition paths between wells. While derived originally for simulations, single-molecule manipulation devices, and in particular optical tweezers, make it possible to use the same methodology also in experiment.