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，并且它们的响应可以作为时间的函数。这些实验从根本上揭示了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。 单分子力谱理论。 在与Szabo博士（NIDDK，NIH）的合作中，我们继续开发形式主义，以从单分子力谱实验中提取准确的动力学和热力学信息。 在这样的分子拉伸实验中，人们可以借助Jarzynski恒等式将测得的力-延伸曲线转化为整个系统的亥姆霍兹自由能。 我们可以展示这些自由能是如何转化为，潜在的分子自由能表面的，这是我们感兴趣的量。目前正在审查这项工作产生的一份文件。 受控分子动力学。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.Phys.2010）。我们发现，粗逆积分，使有效的导航景观地形：逃离当地有效的潜在威尔斯，鞍点的检测，并确定显着的过渡路径之间的威尔斯。虽然最初是为了模拟而衍生的，但单分子操纵设备，特别是光学镊子，使得在实验中也可以使用相同的方法。

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.