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具有序列异质性的分子马达动力学与聚合物易位

Dynamics of molecular motors and polymer translocation with sequence heterogeneity.

作者信息

Kafri Yariv, Lubensky David K, Nelson David R

机构信息

Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.

出版信息

Biophys J. 2004 Jun;86(6):3373-91. doi: 10.1529/biophysj.103.036152.

Abstract

The effect of sequence heterogeneity on polynucleotide translocation across a pore and on simple models of molecular motors such as helicases, DNA polymerase/exonuclease, and RNA polymerase is studied in detail. Pore translocation of RNA or DNA is biased due to the different chemical environments on the two sides of the membrane, whereas the molecular motor motion is biased through a coupling to chemical energy. An externally applied force can oppose these biases. For both systems we solve lattice models exactly both with and without disorder. The models incorporate explicitly the coupling to the different chemical environments for polymer translocation and the coupling to the chemical energy (as well as nucleotide pairing energies) for molecular motors. Using the exact solutions and general arguments, we show that the heterogeneity leads to anomalous dynamics. Most notably, over a range of forces around the stall force (or stall tension for DNA polymerase/exonuclease systems) the displacement grows sublinearly as t(micro), with micro < 1. The range over which this behavior can be observed experimentally is estimated for several systems and argued to be detectable for appropriate forces and buffers. Similar sequence heterogeneity effects may arise in the packing of viral DNA.

摘要

详细研究了序列异质性对多核苷酸跨孔转运以及对诸如解旋酶、DNA聚合酶/核酸外切酶和RNA聚合酶等分子马达简单模型的影响。由于膜两侧不同的化学环境,RNA或DNA的孔转运存在偏向性,而分子马达的运动则通过与化学能的耦合产生偏向性。外部施加的力可以对抗这些偏向性。对于这两个系统,我们精确求解了有无无序情况下的晶格模型。这些模型明确纳入了聚合物转运与不同化学环境的耦合以及分子马达与化学能(以及核苷酸配对能)的耦合。利用精确解和一般性论证,我们表明异质性会导致异常动力学。最值得注意的是,在围绕失速力(或DNA聚合酶/核酸外切酶系统的失速张力)的一系列力范围内,位移随t^μ呈亚线性增长,其中μ<1。针对几个系统估计了可通过实验观察到这种行为的范围,并认为在适当的力和缓冲条件下是可检测到的。类似的序列异质性效应可能出现在病毒DNA的包装中。

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