巨正则重加权分子动力学模拟表明RNA结构探测实验中存在协同效应
Molecular dynamics simulations with grand-canonical reweighting suggest cooperativity effects in RNA structure probing experiments
AI总结：
本研究使用全原子分子动力学模拟，在巨正则系综下开发了一种计算分子亲和力的通用技术，揭示了RNA与SHAPE试剂结合时的协同效应会导致浓度依赖性反应性，并通过新实验进行了定性验证。
摘要：
诸如SHAPE等化学探测实验被常规用于探测RNA分子。在本研究中，我们使用全原子分子动力学模拟来检验以下假设：RNA与SHAPE试剂的结合受到协同效应的影响，从而导致观察到的反应性依赖于试剂浓度。我们开发了一种通用技术，能够在巨正则系综中计算任意分子作为其浓度函数的亲和力。我们对一个RNA结构基序的模拟表明，在SHAPE实验通常使用的浓度下，协同结合将导致可测量的浓度依赖性反应性。我们还通过分析在不同试剂浓度下收集的一组新实验，对该结论提供了定性验证。
英文摘要：
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.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
