Department of Biochemistry, Duke University, Durham, NC 27710, United States; Department of Computer Science, Duke University, Durham, NC 27708, United States.
Department of Computer Science, Duke University, Durham, NC 27708, United States.
J Mol Biol. 2018 Sep 14;430(18 Pt B):3412-3426. doi: 10.1016/j.jmb.2018.06.022. Epub 2018 Jun 18.
The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings, represented as a continuous conformational distribution, and visualized using the disk-on-sphere representation. Using the disk-on-sphere representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions.This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity of Staphylococcus aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing the reorientational components of binding thermodynamics. Such insights allow for the dissection of the dynamic structural components of functionally important intermolecular interactions.
生物大分子的柔韧性是功能的一个重要结构决定因素。不幸的是，离散整体表示法很难捕捉到不同运动模式之间的相关性。在这里，我们提出了新的方法来表示和可视化相关的域间运动。域间运动是直接从残差偶极耦合中确定的，表现为连续的构象分布，并使用磁盘在球体上的表示法进行可视化。使用磁盘在球体上的表示法，可以直观地可视化域间运动的特征，包括相关性。该表示法特别适用于具有广泛构象分布的多域系统。这种分析也可以扩展到多个概率密度模式，使用 Bingham 混合模型。我们使用这个新范例来研究葡萄球菌蛋白 A 的域间运动，它是导致金黄色葡萄球菌致病性的关键毒力因子。我们捕捉到了重要状态之间的平稳过渡，并展示了连续分布函数在计算结合热力学的重定向分量方面的实用性。这种洞察力允许对功能重要的分子间相互作用的动态结构成分进行剖析。
