通过长时间尺度模拟照亮的纳米孔中的蛋白质传输。
Protein Transport through Nanopores Illuminated by Long-Time-Scale Simulations.
机构信息
Institute of Analysis and Scientific Computing, TU Wien, Vienna, 1040, Austria.
Department of Chemistry, Institute of Structural Molecular Biology, University College London, London, WC1E 6BT, United Kingdom.
出版信息
ACS Nano. 2021 Jun 22;15(6):9900-9912. doi: 10.1021/acsnano.1c01078. Epub 2021 Jun 7.
The transport of molecules through nanoscale confined space is relevant in biology, biosensing, and industrial filtration. Microscopically modeling transport through nanopores is required for a fundamental understanding and guiding engineering, but the short duration and low replica number of existing simulation approaches limit statistically relevant insight. Here we explore protein transport in nanopores with a high-throughput computational method that realistically simulates hundreds of up to seconds-long protein trajectories by combining Brownian dynamics and continuum simulation and integrating both driving forces of electroosmosis and electrophoresis. Ionic current traces are computed to enable experimental comparison. By examining three biological and synthetic nanopores, our study answers questions about the kinetics and mechanism of protein transport and additionally reveals insight that is inaccessible from experiments yet relevant for pore design. The discovery of extremely frequent unhindered passage can guide the improvement of biosensor pores to enhance desired biomolecular recognition by pore-tethered receptors. Similarly, experimentally invisible nontarget adsorption to pore walls highlights how to improve recently developed DNA nanopores. Our work can be expanded to pressure-driven flow to model industrial nanofiltration processes.
分子通过纳米受限空间的传输在生物学、生物传感和工业过滤中具有重要意义。为了从根本上理解并指导工程设计,需要通过纳米孔微观模拟传输,但现有的模拟方法持续时间短且复制数量有限,限制了具有统计学意义的深入了解。在这里,我们探索了一种高通量计算方法,该方法通过结合布朗动力学和连续模拟,并整合电渗流和电泳两种驱动力,真实地模拟了数百个甚至长达数秒的蛋白质轨迹,从而实现了在纳米孔中的蛋白质传输。计算了离子电流轨迹以进行实验比较。通过研究三种生物和合成纳米孔,我们的研究回答了关于蛋白质传输的动力学和机制的问题,此外还揭示了实验无法获得但对孔设计相关的见解。频繁无阻的蛋白质传输的发现可以指导生物传感器孔的改进,以增强孔连接的受体对目标生物分子的识别。同样,实验上不可见的非目标吸附到孔壁上突显了如何改进最近开发的 DNA 纳米孔。我们的工作可以扩展到压力驱动的流动,以模拟工业纳滤过程。
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