Jülicher F, Bruinsma R
Institut Curie, Physiocochimie Curie, Section de Recherche, Paris, France.
Biophys J. 1998 Mar;74(3):1169-85. doi: 10.1016/S0006-3495(98)77833-6.
RNA polymerase is a key transcription enzyme that moves along a DNA double helix to polymerize an RNA transcript. Recent progress in micromechanical experiments permits quantitative studies of forces and motion generated by the enzyme. We present in this paper a chemical kinetics description of RNA polymerase motion. The model is based on a classical chemical kinetics description of polymerization reactions driven by a free energy gain that depends on forces applied externally at the catalytic site. The RNA polymerase controlled activation barrier of the reaction is assumed to be strongly dependent on inhibitory internal strains of the RNA polymerase molecule. The sequence sensitivity of RNA polymerase is described by a linear coupling between the height of the activation barrier and the local DNA sequence. Our model can simulate optical trap experiments and allows us to study the dynamics of chemically halted complexes that are important for footprinting studies. We find that the effective stall force is a sequence-dependent, statistical quantity, whose distribution depends on the observation time. The results are consistent with the experimental observations to date.
RNA聚合酶是一种关键的转录酶,它沿着DNA双螺旋移动以聚合RNA转录本。微机械实验的最新进展使得对该酶产生的力和运动进行定量研究成为可能。我们在本文中给出了RNA聚合酶运动的化学动力学描述。该模型基于由自由能增益驱动的聚合反应的经典化学动力学描述,自由能增益取决于在催化位点外部施加的力。假设反应的RNA聚合酶控制的活化能垒强烈依赖于RNA聚合酶分子的抑制性内部应变。RNA聚合酶的序列敏感性通过活化能垒高度与局部DNA序列之间的线性耦合来描述。我们的模型可以模拟光镊实验,并使我们能够研究对足迹研究很重要的化学停滞复合物的动力学。我们发现有效停滞力是一个依赖于序列的统计量,其分布取决于观察时间。结果与迄今为止的实验观察结果一致。