报告题目:计算显微镜下的实例：光捕获机制与抗生素跨膜孔道转运

报告人:Ulrich Kleinekathöfe

报告时间:2025年6月6日15：00-17：00

报告地点:数理楼403

报告对象:全校感兴趣师生

主办单位:黑料社区

报告人简介:Ulrich Kleinekathöfer，德国Constructor University理黑料社区 理论物理学教授。Ulrich Kleinekathöfer教授于1996年在德国Max-Planck-Institute for Fluid Dynamics获得博士学位，研究方向为范德华小分子计算研究；随后在以色列Weizmann Institute of Science担任博士后；2002年开始在德国Chemnitz University of Technology任教；自2006年起，担任德国Constructor University理黑料社区 理论物理学教授。研究方向是生物分子复合物的经典和量子动力学研究，包括通过纳米孔道渗透、光合作用以及电荷传输。在Cell, Nature Microbiology, Chemical Reviews, Nature Communications, JACS, Science Advances, Angewandte Chemie等学术期刊发表研究论文180余篇，被引用＞6000次。

报告内容简介:In many applications such as DNA or protein sequencing and sensing, voltage-dependent transport through biological and artificial nanopores is being used. The electroosmotic flow (EOF) is a voltage-dependent ion-associated flow of solvent molecules, i.e., usually water, and depends on many factors, such as pH, temperature, pore diameter, and also the concentration of ions. The exact interplay between these factors is so far poorly understood. In a joint experimental and computational study, we have investigated the dependence of the EOF on the concentration of the buffer salt by probing the transport of α-cyclodextrin molecules through the ΔCymA channel. To our surprise, the concentration-dependent net ionic flux changes non-monotonically and nonlinearly and the EOF is seen to follow the same pattern. Thus, the effect of the EOF has to be taken into account in the future when analyzing experimental, e.g., when discriminating chiral isomers using nanopores.

In the talk, I will also briefly touch on another line of research in our research lab which focuses on the molecular mechanism of antibiotics translocation through bacterial channels. The presence of loop stabilization networks in porins suggests that the conformational dynamics of the constriction loop, e.g. in OmpF, is possibly of importance. A molecular mechanism of permeation is put forward wherein charged antibiotics perturb the network of stabilizing hydrogen-bond interactions and induce conformational changes in the L3 segment, thereby aiding the permeation of bulky antibiotic molecules across the constriction region.

在DNA或蛋白质测序及传感等众多应用中，基于生物与人工纳米孔的电压依赖性输运技术正被广泛采用。电渗流（EOF）是一种电压依赖性的、与离子关联的溶剂分子（通常为水）流动现象，其强度受pH值、温度、孔径及离子浓度等多重因素影响。迄今为止，这些因素间的精确相互作用机制尚不明确。通过一项联合实验与计算研究，我们以α-环糊精分子在ΔCymA通道中的输运为探针，探究了EOF对缓冲盐浓度的依赖性。令人惊讶的是，浓度依赖的净离子通量呈现非单调非线性变化，且EOF被观察到遵循相同规律。因此，在未来分析实验数据时（例如使用纳米孔鉴别手性异构体），必须充分考虑EOF的影响。

在报告中，我将简要提及本实验室另一研究方向：抗生素穿越细菌通道的分子机制。孔蛋白中存在的环区稳定化网络表明，限域环（如OmpF中的L3环）的构象动力学可能具有关键作用。我们提出一种渗透分子机制：带电抗生素扰动稳定氢键相互作用网络，诱导L3片段的构象变化，从而促进大分子抗生素穿越限域区域。