Heal Jack W, Wells Stephen A, Blindauer Claudia A, Freedman Robert B, Römer Rudolf A
MOAC Doctoral Training Centre, University of Warwick, Coventry, United Kingdom; Institute for Advanced Study, University of Warwick, Coventry, United Kingdom.
Department of Chemistry, University of Bath, Bath, United Kingdom.
Biophys J. 2015 Apr 7;108(7):1739-1746. doi: 10.1016/j.bpj.2015.02.017.
Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically. We have obtained HDX data for the complex of cyclophilin A with the immunosuppressant cyclosporin A. We compare these data, as well as literature values for uncomplexed cyclophilin A, to theoretical predictions using a combination of rigidity analysis and coarse-grained simulations of protein motion. We find that in this case, the most specific prediction of folding cores comes from a combined approach that models the rigidity of the protein using the first software suite and the dynamics of the protein using the froda tool.
确定蛋白质的折叠核心可提供有关其折叠过程和动力学的信息。识别构成折叠核心的氨基酸的实验方法包括氢-氘交换和Φ值分析，这些方法可能既昂贵又耗时。因此，人们希望在理论上改进现有的确定蛋白质折叠核心的方法。我们获得了亲环蛋白A与免疫抑制剂环孢菌素A复合物的氢-氘交换数据。我们将这些数据以及未复合的亲环蛋白A的文献值与使用蛋白质运动的刚性分析和粗粒度模拟相结合的理论预测进行比较。我们发现，在这种情况下，对折叠核心最具体的预测来自一种组合方法，该方法使用第一个软件套件对蛋白质的刚性进行建模，并使用froda工具对蛋白质的动力学进行建模。
