Physics Department, Technical University of Munich, Garching, Germany.
Biophys J. 2012 May 16;102(10):2321-30. doi: 10.1016/j.bpj.2012.04.008. Epub 2012 May 15.
Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so-called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain.
转录因子（TFs），如乳糖阻遏物，能够以极高的效率在 DNA 上找到其靶序列。在 Berg-von Hippel 建立的搜索过程模型中，TF 在三维溶液扩散和沿 DNA 链一维滑动之间交替进行。为了克服所谓的速度-稳定性悖论，在类似的模型中，TF 被认为存在两种构象（搜索状态和识别状态），它们之间随机切换。我们结合了促进扩散模型和交替状态，得到了一个广义模型。我们明确地处理了平行排列的棒状链的体相跃迁，并考虑了一个简化的卷曲 DNA 模型。与之前考虑的促进扩散模型相比，它们对应于我们广义模型的极限情况，我们令人惊讶地发现靶标搜索率降低了。此外，在最佳条件下，蛋白质在 DNA 链上和链外的停留时间不再均等分配。
