Determining Atomistic SAXS Models of Tri-Ubiquitin Chains from Bayesian Analysis of Accelerated Molecular Dynamics Simulations
Determining Atomistic SAXS Models of Tri-Ubiquitin Chains from Bayesian Analysis of Accelerated Molecular Dynamics Simulations
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DOI：
10.1021/acs.jctc.7b00059
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发表时间：
2017-06-01
影响因子：
5.5
通讯作者：
Wereszczynski, Jeff
中科院分区：
文献类型：
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作者：
Bowerman, Samuel;Rana, Ambar S. J. B.;Wereszczynski, Jeff
小角x射线散射（SAXS）已成为表征柔性生物分子溶液系的一种日益流行的技术。然而，SAXS产生的数据通常是低维的，因此在没有额外的结构知识的情况下很难解释。理论上，分子动力学（MD）轨迹可以提供这些信息，但传统的模拟很少采样完整的集合。在这里，我们证明了加速MD模拟可以在比标准模拟更短的时间尺度内产生更高质量的模型，并且我们提出了一种迭代贝叶斯蒙特卡罗方法，能够在没有过拟合的情况下识别多状态集成。该方法应用于几种泛素三聚体，以证明连锁类型对信号蛋白溶液状态的影响。我们观察到，连接位点直接影响三聚体的溶液灵活性，并推测这种可塑性的差异导致了它们在体内的不同作用。
Small-angle X-ray scattering (SAXS) has become an increasingly popular technique for characterizing the solution ensemble of flexible biomolecules. However, data resulting from SAXS is typically low-dimensional and is therefore difficult to interpret without additional structural knowledge. In theory, molecular dynamics (MD) trajectories can provide this information, but conventional simulations rarely sample the complete ensemble. Here, we demonstrate that accelerated MD simulations can be used to produce higher quality models in shorter time scales than standard simulations, and we present an iterative Bayesian Monte Carlo method that is able to identify multistate ensembles without overfitting. This methodology is applied to several ubiquitin trimers to demonstrate the effect of linkage type on the solution states of the signaling protein. We observe that the linkage site directly affects the solution flexibility of the trimer and theorize that this difference in plasticity contributes to their disparate roles in vivo.