Colocalization single-molecule methods can provide a wealth of information concerning the ordering and dynamics of biomolecule assembly. These have been used extensively to study the pathways of spliceosome assembly in vitro. Key to these experiments is the measurement of binding times-either the dwell times of a multi-molecular interaction or times in between binding events. By analyzing hundreds of these times, many new insights into the kinetic pathways governing spliceosome assembly have been obtained. Collections of binding times are often plotted as histograms and can be fit to kinetic models using a variety of methods. Here, we describe the use of maximum likelihood methods to fit dwell time distributions without binning. In addition, we discuss several aspects of analyzing these distributions with histograms and pitfalls that can be encountered if improperly binned histograms are used. We have automated several aspects of maximum likelihood fitting of dwell time distributions in the AGATHA software package.

中文翻译：

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通过停留时间分布的最大似然拟合分析剪接体动力学

共定位单分子方法可以提供大量有关生物分子组装顺序和动力学的信息。这些已被广泛用于研究体外剪接体组装的途径。这些实验的关键是结合时间的测量——多分子相互作用的停留时间或结合事件之间的时间。通过对数百次这样的分析，获得了许多关于控制剪接体组装的动力学途径的新见解。结合时间的集合通常绘制为直方图，可以使用各种方法拟合动力学模型。在这里，我们描述了使用最大似然方法来拟合驻留时间分布而不进行分箱。此外，我们讨论了使用直方图分析这些分布的几个方面，以及如果使用不正确的分箱直方图可能会遇到的陷阱。我们已经在 AGATHA 软件包中自动化了停留时间分布的最大似然拟合的几个方面。