论文标题
基于非平衡溶液的单分子FRET数据的最大似然分析
Maximum likelihood analysis of non-equilibrium solution-based single-molecule FRET data
论文作者
论文摘要
测量自由扩散单分子的Förster共振能量转移（FRET）效率提供了有关分子采样构象状态的信息。在平衡条件下，构象状态的分布与时间无关，而在非平衡条件下它会随着时间而变化。在这项工作中，我们考虑了基于非平衡溶液的单分子fret数据的参数推断问题。借助用于构象动力学的非平衡模型和依赖构象的FRET效率分布的模型，可以构建可能性函数。模型参数，例如非平衡构象动力学模型的速率常数和不同构象状态的平均货物效率，通过通过数据最大化适当的可能性函数来估计，从数据中估算了预期最大化函数。我们说明了一些简单的非平衡模型的可能性方法，并通过模拟验证了该方法。可能的方法可以应用于研究蛋白质折叠，大分子复合物的形成，蛋白质构象动力学和单分子水平和溶液中的其他非平衡过程。
Measuring the Förster resonance energy transfer (FRET) efficiency of freely diffusing single molecules provides information about the sampled conformational states of the molecules. Under equilibrium conditions, the distribution of the conformational states is independent of time, whereas it can vary over time under non-equilibrium conditions. In this work, we consider the problem of parameter inference on non-equilibrium solution-based single-molecule FRET data. With a non-equilibrium model for the conformational dynamics and a model for the conformation-dependent FRET efficiency distribution, the likelihood function could be constructed. The model parameters, such as the rate constants of the non-equilibrium conformational dynamics model and the average FRET efficiencies of the different conformational states, have been estimated from the data by maximizing the appropriate likelihood function via the Expectation-Maximization algorithm. We illustrate the likelihood method for a few simple non-equilibrium models and validated the method by simulations. The likelihood method could be applied to study protein folding, macromolecular complex formation, protein conformational dynamics and other non-equilibrium processes at the single-molecule level and in solution.
