Due to the sequence-dependent nature of the elasticity of DNA, many protein-DNA complexes and other systems in which DNA molecules must be deformed have preferences for the type of DNA sequence they interact with. SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments and similar sequence selection experiments have been used extensively to examine the (indirect readout) sequence preferences of, e.g., nucleosomes (protein spools around which DNA is wound for compactification) and DNA rings. We show how recently developed computational and theoretical tools can be used to emulate such experiments in silico. Opening up this possibility comes with several benefits. First, it allows us a better understanding of our models and systems, specifically about the roles played by the simulation temperature and the selection pressure on the sequences. Second, it allows us to compare the predictions made by the model of choice with experimental results. We find agreement on important features between predictions of the rigid base-pair model and experimental results for DNA rings and interesting differences that point out open questions in the field. Finally, our simulations allow application of the SELEX methodology to systems that are experimentally difficult to realize because they come with high energetic costs and are therefore unlikely to form spontaneously, such as very short or overwound DNA rings.

中文翻译：

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在计算机上执行SELEX实验

由于DNA弹性的序列依赖性，许多蛋白质-DNA复合物和其他必须使DNA分子变形的系统对它们相互作用的DNA序列的类型有偏爱。SELEX（通过指数富集的配体的系统进化）实验和类似的序列选择实验已广泛用于检查（例如，核小体（DNA绕其缠绕以进行压缩的蛋白质线轴））和DNA环的（间接读出）序列偏好。我们展示了如何利用最新开发的计算和理论工具在计算机模拟这些实验。打开这种可能性有几个好处。首先，它使我们可以更好地了解我们的模型和系统，尤其是关于模拟温度和序列选择压力所起的作用。其次，它使我们能够将所选模型的预测结果与实验结果进行比较。我们发现在刚性碱基对模型的预测与DNA环的实验结果之间的重要特征上达成了一致，并且有趣的差异指出了该领域尚待解决的问题。最后，我们的仿真允许将SELEX方法应用于在实验上难以实现的系统，因为它们的能源成本很高，因此不太可能自发形成，例如非常短或过长的DNA环。