With rapid advancement in the fields of nanopore analysis of protein, it has become imperative to develop modeling framework for understanding the protein dynamics in nanopores. Such modeling framework should include the effects of electro-osmosis, as it plays significant role during protein translocation in confinement. Currently, the molecular dynamics simulations that include the hydrodynamic effects are limited to a timescale of few 100 ns. These simulations give insight about important events like protein unfolding which occurs in this timescale. But many electrophoresis experiments are limited by a detector resolution of approximately 2.5 microseconds. Analytical theory has been used to interpret protein dynamics at such large timescale. There is a need for molecular modeling of more complex environment and protein shapes which cannot be accounted for by analytical theory. We have developed a framework to study globular protein dynamics in nanopores by using langevin dynamics on a rigid body model of protein and the hydrodynamics is accounted by analytical theory for simple cylindrical nanopore geometry. This framework has been applied to study the dynamics of Ubiquitin translocation in SiNx nanopore by Nir et al. They have reported 7 times decrease in average dwell time of the protein inside the nanopore in response to a small change in pH from 7.0 to 7.2 and the modification of protein charge was attributed for such drastic change. Closer examination using our simulation revealed that the electro-osmotic effects originating due to very small change in the surface electrostatic potential of the nanopore could lead to such a drastic change in protein dynamics.

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微秒时间尺度纳米孔中蛋白质动力学的朗之万动力学模拟

随着蛋白质纳米孔分析领域的快速发展，开发用于理解纳米孔中蛋白质动力学的建模框架已成为当务之急。这种建模框架应包括电渗透的影响，因为它在禁闭中的蛋白质易位过程中发挥着重要作用。目前，包括流体动力学效应在内的分子动力学模拟仅限于几个 100 ns 的时间尺度。这些模拟提供了有关在此时间尺度上发生的蛋白质展开等重要事件的见解。但是，许多电泳实验受限于大约 2.5 微秒的检测器分辨率。分析理论已被用于在如此大的时间尺度上解释蛋白质动力学。需要对分析理论无法解释的更复杂的环境和蛋白质形状进行分子建模。我们开发了一个框架，通过在蛋白质的刚体模型上使用朗之万动力学来研究纳米孔中的球状蛋白质动力学，流体动力学由简单圆柱形纳米孔几何形状的分析理论解释。该框架已被 Nir ​​等人应用于研究 SiNx 纳米孔中泛素易位的动力学。他们报告说，响应 pH 从 7.0 到 7.2 的微小变化，纳米孔内蛋白质的平均停留时间减少了 7 倍，蛋白质电荷的改变归因于这种剧烈变化。