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存在陷阱时蛋白质在DNA上寻找靶标的动力学。

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps.

作者信息

Lange Martin, Kochugaeva Maria, Kolomeisky Anatoly B

机构信息

Department of Chemistry, Rice University , Houston, Texas 77005, United States.

Johannes Gutenberg University , Mainz 55122, Germany.

出版信息

J Phys Chem B. 2015 Sep 24;119(38):12410-6. doi: 10.1021/acs.jpcb.5b07303. Epub 2015 Sep 14.

Abstract

Protein search for specific binding sites on DNA is a fundamental biological phenomenon associated with the beginning of most major biological processes. It is frequently found that proteins find and recognize their specific targets quickly and efficiently despite the complex nature of protein-DNA interactions in living cells. Although significant experimental and theoretical efforts were made in recent years, the mechanisms of these processes remain not well-clarified. We present a theoretical study of the protein target search dynamics in the presence of semispecific binding sites which are viewed as traps. Our theoretical approach employs a discrete-state stochastic method that accounts for the most important physical and chemical processes in the system. It also leads to a full analytical description for all dynamic properties of the protein search. It is found that the presence of traps can significantly modify the protein search dynamics. This effect depends on the spatial positions of the targets and traps, on distances between them, on the average sliding length of the protein along the DNA, and on the total length of DNA. Theoretical predictions are discussed using simple physical-chemical arguments, and they are also validated with extensive Monte Carlo computer simulations.

摘要

蛋白质寻找DNA上的特异性结合位点是一种基本的生物学现象,与大多数主要生物学过程的起始相关。经常发现,尽管活细胞中蛋白质与DNA相互作用具有复杂性,但蛋白质能够快速且高效地找到并识别其特异性靶点。尽管近年来进行了大量的实验和理论研究,但这些过程的机制仍未得到充分阐明。我们对存在半特异性结合位点(被视为陷阱)时蛋白质的靶点搜索动力学进行了理论研究。我们的理论方法采用离散状态随机方法,该方法考虑了系统中最重要的物理和化学过程。它还能对蛋白质搜索的所有动态特性进行完整的解析描述。研究发现,陷阱的存在可显著改变蛋白质的搜索动力学。这种效应取决于靶点和陷阱的空间位置、它们之间的距离、蛋白质沿DNA的平均滑动长度以及DNA的总长度。使用简单的物理化学论据对理论预测进行了讨论,并且还通过广泛的蒙特卡罗计算机模拟对其进行了验证。

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