An interdisciplinary approach to model the interaction and binding of flexible proteins: Applications to SARS-CoV-2 accessory proteins'

蛋白质的动力学对蛋白质的功能和相互作用起着至关重要的作用。传统的结构生物学提供了有限的见解，高度灵活，但功能，区域，因为这些在大多数晶体和低温电镜结构中是不存在的。核磁共振波谱，分子动力学模拟和分子生物学将结合在这个项目中，以表征柔性蛋白质如何与它们的结合伙伴相互作用。重点将放在糖蛋白血管性血友病因子及其结合伙伴上，例如因子VIII，其中无序的a3结构域对于高亲和力结合至关重要。这个项目是高度跨学科的，涉及计算建模、核磁共振和湿实验室的大量元素。

The dynamics of proteins play critical roles for functions and interactions. Traditionalstructural biology provides limited insights on highly flexible, yet functional, regions sincethese are absent in most crystal- and cryo-EM structures. NMR spectroscopy, moleculardynamics simulations and molecular biology will be combined in this project to characterisehow flexible proteins interact with their binding partners. Focus will be on the bloodglycoprotein von Willebrand factor and its binding partners, for example Factor VIII, wherethe disordered a3 domain is imperative for high-affinity binding. This project is highlyinterdisciplinary, involving substantial elements of computational modelling, NMR and wet-labwork.