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Facilitated search of proteins on DNA: correlations are important

机译：促进DNA上蛋白质的搜索：相关性很重要

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摘要

A starting point of many biological processes is protein binding to specific regions on DNA. Although typical concentrations of DNA-binding proteins are low, and target sites are typically buried among huge number of non-specific sites, the search process is frequently achieved at a remarkably fast rate. For some proteins it has been confirmed that association rates might be even larger than the maximal allowed three-dimensional diffusion rates. The current theoretical view of this phenomenon is based on the idea of lowering dimensionality, i.e., the overall search process is viewed as a combination of uncorrelated three-dimensional excursions in the solution and one-dimensional hoppings on DNA. However, some predictions of this theoretical picture contradict recent single-molecule measurements of protein diffusion processes. An alternative theoretical approach points out the importance of correlations during the search process that appear due to non-specific interactions between protein and DNA molecules. To test different theoretical ideas we performed extensive lattice Monte Carlo computer simulations of the facilitated diffusion. Our results revealed that correlations are important, and the acceleration in the search could only be achieved at some intermediate non-specific binding energies and protein concentrations. Physico-chemical aspects and the origins of these correlations are discussed.
机译：许多生物学过程的起点是蛋白质与DNA特定区域的结合。尽管DNA结合蛋白的典型浓度较低，并且目标位点通常埋在大量的非特异性位点中，但搜索过程通常以非常快的速度实现。对于某些蛋白质，已经证实缔合速率可能甚至大于允许的最大三维扩散速率。当前对该现象的理论观点是基于降低维数的想法，即，整个搜索过程被视为溶液中不相关的三维偏移和DNA的一维跳跃的组合。但是，此理论图的某些预测与蛋白质扩散过程的最新单分子测量相矛盾。一种替代的理论方法指出了在搜索过程中相关性的重要性，这种相关性是由于蛋白质和DNA分子之间的非特异性相互作用而出现的。为了测试不同的理论思想，我们对促进扩散进行了广泛的蒙特卡罗计算机模拟。我们的结果表明相关性很重要，并且仅在某些中间非特异性结合能和蛋白质浓度下才能实现搜索加速。讨论了理化方面以及这些相关性的起源。

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