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DNA-蛋白质相互作用和促进扩散的动力学和动力学生物模型比较。

Comparison of kinetic and dynamical models of DNA-protein interaction and facilitated diffusion.

机构信息

Laboratoire de Spectrométrie Physique (CNRS UMR 5588), Université Joseph Fourier - Grenoble 1, BP 87, 38402 St. Martin d'Hères, France.

出版信息

J Phys Chem A. 2010 Sep 16;114(36):9662-72. doi: 10.1021/jp101151a.

Abstract

It has long been asserted that proteins such as transcription factors may locate their target in DNA sequences at rates that surpass by several orders of magnitude the three-dimensional diffusion limit thanks to facilitated diffusion, that is, the combination of one-dimensional (sliding along the DNA) and three-dimensional diffusion. This claim has been supported throughout the years by several mass action kinetic models, while the dynamical model we proposed recently (J. Chem. Phys. 2009, 130, 015103) suggests that acceleration of targeting due to facilitated diffusion cannot be large. In order to solve this apparent contradiction, we performed additional simulations to compare the results obtained with our model to those obtained with the kinetic model of Klenin et al. (Phys. Rev. Lett. 2006, 96, 018104). We show in this paper that the two models actually support each other and agree in predicting a low efficiency for facilitated diffusion. Extrapolation of these results to real systems even indicates that facilitated diffusion necessarily slows down the targeting process compared to three-dimensional diffusion.

摘要

长期以来,人们一直断言,转录因子等蛋白质可以通过易化扩散(即一维(沿 DNA 滑动)和三维扩散的组合)以超过三维扩散限制几个数量级的速度定位其在 DNA 序列中的靶标。多年来,这一说法得到了几个质量作用动力学模型的支持,而我们最近提出的动力学模型(J. Chem. Phys. 2009, 130, 015103)表明,由于易化扩散而导致的靶向加速不可能很大。为了解决这一明显的矛盾,我们进行了额外的模拟,以比较我们的模型与 Klenin 等人的动力学模型(Phys. Rev. Lett. 2006, 96, 018104)得出的结果。我们在本文中表明,这两个模型实际上是相互支持的,并一致预测易化扩散的效率很低。将这些结果外推到实际系统中甚至表明,与三维扩散相比,易化扩散必然会减缓靶向过程。

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