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DNA-蛋白质结合速率:弯曲波动和流体动力学耦合效应。

DNA-protein binding rates: bending fluctuation and hydrodynamic coupling effects.

机构信息

Department of Physics, Technical University of Munich, 85748 Garching, Germany.

出版信息

J Chem Phys. 2010 Apr 7;132(13):135103. doi: 10.1063/1.3352571.

Abstract

We investigate diffusion-limited reactions between a diffusing particle and a target site on a semiflexible polymer, a key factor determining the kinetics of DNA-protein binding and polymerization of cytoskeletal filaments. Our theory focuses on two competing effects: polymer shape fluctuations, which speed up association, and the hydrodynamic coupling between the diffusing particle and the chain, which slows down association. Polymer bending fluctuations are described using a mean field dynamical theory, while the hydrodynamic coupling between polymer and particle is incorporated through a simple heuristic approximation. We validate both of these through comparison to Brownian dynamics simulations. Neither of the effects has been fully considered before in the biophysical context and we show they are necessary to form accurate estimates of reaction processes. The association rate depends on the stiffness of the polymer and the particle size, exhibiting a maximum for intermediate persistence length and a minimum for intermediate particle radius. In the parameter range relevant to DNA-protein binding, the rate increase is up to 100% compared with the Smoluchowski result for simple center-of-mass motion. The quantitative predictions made by the theory can be tested experimentally.

摘要

我们研究了扩散粒子与半柔性聚合物上靶位之间的扩散限制反应,这是决定 DNA-蛋白质结合动力学和细胞骨架丝聚合的关键因素。我们的理论集中于两种竞争效应:聚合物形状波动,加速了结合;扩散粒子与链之间的流体动力耦合,减缓了结合。聚合物弯曲波动使用平均场动力学理论来描述,而聚合物与粒子之间的流体动力耦合则通过简单的启发式近似来包含。我们通过与布朗动力学模拟的比较来验证这两种方法。在生物物理背景下,以前都没有完全考虑到这两种效应,我们表明它们对于形成反应过程的准确估计是必要的。结合速率取决于聚合物的刚度和粒子的大小,在中等持久长度和中等粒子半径处表现出最大值。在与 DNA-蛋白质结合相关的参数范围内,与简单质心运动的 Smoluchowski 结果相比,速率增加高达 100%。该理论的定量预测可以通过实验来检验。

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