DYNAMIC COUPLING AND BINDING IN A GTPASE - EFFECTOR COMPLEX

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 MD模拟为蛋白质-蛋白质相互作用提供了新的见解;蛋白质结合/解离事件以及在细胞信号蛋白中看到的跨界面的结构和动力学变化的耦合。丛蛋白-B1是一种跨膜受体，对神经元和心血管发育至关重要，但在癌症扩散（转移）中也至关重要。胞内结构域直接与小GTP酶Rac 1和Rnd 1相互作用。我们正在进行一项广泛的实验和计算项目，以了解这种相互作用，并在Aton上寻找时间，将我们的模拟推进到多微秒的时间尺度，以研究丛蛋白-B1/GTdR复合物的结构和动力学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MD simulations provide new insights into protein-protein interactions; protein binding/dissociation events and the coupling of structural and dynamical changes across interfaces that is seen in cell signaling proteins. Plexin-B1 is a transmembrane receptor critical for neuronal and cardiovascular development, but also in cancer spreading (metastasis). An intracellular domain interacts directly with the small GTPases Rac1 and Rnd1. We are in the middle of an extensive experimental and computational project to understand this interaction and seek time on Aton to push our simulations into the multi-microsecond timescale to study the structure and dynamics of the plexin-B1/GTPase complexes.