论文标题
带有宏伟的典型重新加权的分子动力学模拟在RNA结构探测实验中提示合作效应
Molecular dynamics simulations with grand-canonical reweighting suggest cooperativity effects in RNA structure probing experiments
论文作者
论文摘要
化学探测实验（例如形状）通常用于探测RNA分子。在这项工作中，我们使用原子分子动力学模拟来检验以下假设：RNA与形状试剂的结合受合作效应的影响，导致观察到的反应性取决于试剂浓度。我们开发了一种通用技术，该技术可以计算对任意分子的亲和力，这是它们在大型典型集合中的浓度的函数。我们对RNA结构基序的模拟表明，在形状实验中通常使用的浓度下，合作结合将导致可测量的浓度依赖性反应性。我们还通过分析以不同的试剂浓度收集的一组新的实验来提供对该陈述的定性验证。
Chemical probing experiments such as SHAPE are routinely used to probe RNA molecules. In this work, we use atomistic molecular dynamics simulations to test the hypothesis that binding of RNA with SHAPE reagents is affected by cooperative effects leading to an observed reactivity that is dependent on the reagent concentration. We develop a general technique that enables the calculation of the affinity for arbitrary molecules as a function of their concentration in the grand-canonical ensemble. Our simulations of an RNA structural motif suggest that, at the concentration typically used in SHAPE experiments, cooperative binding would lead to a measurable concentration-dependent reactivity. We also provide a qualitative validation of this statement by analyzing a new set of experiments collected at different reagent concentrations.
