ensemble descriptions of disordered proteins and their complexes

蛋白质就像一串串珠子，在这种情况下是由不同类型的氨基酸残基组成的链。虽然许多蛋白质为了发挥功能而采用相对静态和有序的三维形状，但最近已经清楚的是，一大类“无序”蛋白质并非如此。它们以高度灵活的状态发挥作用，主要是与其他蛋白质结合。结合后，一些无序的蛋白质确实会变得有序，但另一些蛋白质则保持了很大的灵活性。无序蛋白质在从病毒到植物和动物的整个生物学中都有发现，与控制关键生物事件和疾病有关。为了更好地了解这些蛋白质的性质和它们执行的生物学行为，对无序蛋白质及其动态复合体的真实描述是必不可少的。虽然静态蛋白质需要一种结构来描述它，但无序的蛋白质或动态复合体需要许多结构(集合)来表示它，这是标准结构方法所不可能做到的。因此，我们一直在开发计算机方法集合，计算与大量实验数据一致并一起代表无序蛋白质的结构集合。这种方法的许多方面必须进一步发展，因为没有足够的数据来定义集合，而且在数据的解释和算法的优化方面存在问题。因此，我们提出了以下目标：(1)开发集成以更好地表征分离的无序蛋白。使用模型系统，我们将获得实验数据，并探索更好的方法从其中提取结构信息，执行不同类型的计算模拟，并确定在系综中使用的最佳算法。(2)发展表征无序蛋白质复合体的方法。使用不同的模型系统，将探索新的方法，以减少由于动态络合物中的运动而导致的核磁共振数据较差的问题，并扩展系综描述动态络合物的能力。我们的努力将提供一个强大的工具，将广泛适用于结构社区研究这一重要但具有挑战性的高动态蛋白质类别。

Proteins are like strands of beads, in this case made up of a chain of different types of amino acid residues. While many proteins adopt a relatively static and ordered 3-dimensional shape in order to function, it has become clear recently that a large class of "disordered" proteins do not. They function in a highly flexible state, primarily in binding to other proteins. Upon binding, some disordered proteins do become ordered but others retain much of their flexibility. Disordered proteins are found throughout biology, from viruses to plants and animals, and are associated with controlling critical biological events as well as in disease. In order to better understand the nature of these proteins and the biology they perform, realistic descriptions of disordered proteins and their dynamic complexes are essential. While a static protein needs one structure to describe it, a disordered protein or dynamic complex requires many structures (an ensemble) to represent it, not possible with standard structural approaches. Thus, we have been developing the computer approach ENSEMBLE that calculates collections of structures that together are consistent with a large amount of experimental data and together represent the disordered protein. Many aspects of this approach must be further developed since there is not enough data to define the ensemble and there are issues with the interpretation of the data and the optimization of the algorithm. Thus, we propose the following aims: (1) Develop ENSEMBLE to better characterize isolated disordered proteins. Using a model system, we will obtain experimental data and explore better ways to extract structural information from them, perform different types of computational simulations and determine the best algorithms to utilize within ENSEMBLE. (2) Develop approaches to characterize complexes of disordered proteins. Using a different model system, will explore new methods to reduce problems with poor NMR data due to motion in dynamic complexes and expand ENSEMBLE's capability to describe dynamic complexes. Our efforts will provide a powerful tool that will be widely available to the structural community for studying this important yet challenging class of highly dynamic proteins.