Multiscale Computer Simulation of Key Biomolecular Processes in the Cell

项目摘要 蛋白质相互作用、自组装、膜靶向和重塑是密切相关的 与许多重要的细胞现象有关，包括内吞作用、感染、免疫反应、细胞器 形成、细胞分裂、信号和运动。这些过程天生就是多尺度的，因为它们跨越了 从分子到纳米再到介观的时间和长度尺度。例如，分子层面的 蛋白质集合和脂膜之间的相互作用可以对大的 鳞片膜形态。同样，肌动蛋白和肌动蛋白结合蛋白相互作用的原子细节 传播到更长的长度和时间尺度，涉及细胞中的蛋白质组装过程 细胞骨架。因此，这个项目的主要科学前提是，在一个耦合的过程中进行研究是至关重要的 跨越多个尺度的时尚，局部分子相互作用在尺度上向上传播到集体 在细胞水平上的行为。研究涉及到小说的持续发展和应用 多尺度、粗粒度的计算方法，非常适合研究集体 在关键细胞现象的背景下，蛋白质与其他蛋白质和膜的相互作用 本研究的主要目的有两个：(1)新的多尺度的持续发展 可用于研究大规模蛋白质和蛋白质的日益复杂的方面的模拟方法 蛋白质介导的膜过程，以及(2)关键蛋白质靶向的机制的阐述 和重塑现实的生物膜，以及蛋白质如何相互作用和自我组装 细胞骨架和细胞骨架-膜界面。与领先的实验公司合作 研究人员表示，多尺度模拟的应用将包括对真实膜模型的研究， 蛋白质介导的膜和肌动蛋白细丝的重塑，肌动蛋白细丝与外周的相互作用 膜蛋白对膜曲率的调节以及高度有序的外壳蛋白诱导的机制 膜重塑。这项研究的总体长期目标是继续开发和应用 研究现实生物分子现象的强大而系统的多尺度计算方法 对各种细胞现象具有重要意义。

Project Summary Protein-protein interactions, self-assembly, and membrane targeting and remodeling are intimately associated with many critical cellular phenomena, including endocytosis, infection, immune response, organelle formation, cell division, signaling, and movement. These processes are innately multiscale, as they span from the molecular to nanoscopic to mesoscopic time and length scales. For instance, the molecular-level interactions between collections of proteins and the lipid membrane can have a profound effect on the large scale membrane morphology. Likewise, the atomistic details of actin and actin-binding protein interactions propagate to much longer length and time scales involving protein assembly processes in the cellular cytoskeleton. Therefore, the main scientific premise of this project is that it is critical to study, in a coupled fashion across multiple scales, the propagation of local molecular interactions upward in scale to the collective behavior at the cellular level. The research involves the continued development and application of novel multiscale, coarse-grained computational methods that are ideally suited to investigate the collective interactions of proteins with other proteins and with membranes, within the context of key cellular phenomena There are two main overarching aims of this research: (1) the continued development of new multiscale simulation methods that can be utilized to study increasingly complex aspects of large scale protein-protein and protein-mediated membrane processes, and (2) the elaboration of the mechanisms by which key proteins target and remodel realistic biological membranes, and how proteins interact and self-assemble with one another in the cytoskeleton and at the cytoskeleton-membrane interface. In collaboration with leading experimental researchers, the applications of the multiscale simulations will include studies of realistic membrane models, protein-mediated remodeling of membranes and actin filaments, the interaction of actin filaments with peripheral membrane proteins to regulate membrane curvature, and the mechanism of highly ordered coat protein-induced membrane remodeling. The overarching long term goal of this research is to continue to develop and apply a powerful and systematic multiscale computational approach for the study of realistic biomolecular phenomena of significant importance to various cellular phenomena.