A New Method for Biomembrane Simulations

项目摘要 膜靶向和重塑与许多重要的细胞现象密切相关， 包括内吞作用、感染、免疫反应、细胞器形成、细胞分裂、信号和 有动静。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 时间和长度的介观尺度。例如，分子水平的相互作用之间的集合 蛋白质和脂双分子层对大尺度膜的形态有深远的影响。主 这个项目的科学前提是，至关重要的是，以一种跨多个尺度的耦合方式研究 局部分子相互作用在尺度上向上传播到集体和紧急行为 介观层面。因此，本项目涉及到小说的继续开发和应用 最适合研究蛋白质集体相互作用的多尺度计算方法 有膜的。 本研究主要包括两个部分：(1)新的多尺度模拟的发展 可用于研究大规模蛋白质介导膜日益复杂的方面的方法 过程，以及(2)关键蛋白质靶向和重塑生物的机制的阐述 膜。将研究三类蛋白质-膜系统：外周膜蛋白( Bar结构域家族及其如何重塑膜)、跨膜蛋白(流感M2蛋白和 在病毒萌发过程中，它如何与膜相互作用以产生膜弯曲)，以及 信号蛋白(PKC、PDK1和AKT1)，以帮助阐明在 通过这些蛋白质的膜靶向和结合。这项研究的总体长期目标是 继续开发和应用强大和系统的多尺度计算方法来研究 真实的蛋白质介导膜现象。

Project Summary Membrane targeting and remodeling is 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 the nanoscopic to the mesoscopic time and length scales. For instance, the molecular-level interactions between collections of proteins and the lipid bilayer can have a profound effect on the large scale membrane morphology. 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 and emergent behavior at the mesoscopic level. This project therefore involves the continued development and application of novel multiscale computational methods that are ideally suited to investigate the collective interactions of proteins with membranes. There are two main components of this research: (1) the development of new multiscale simulation methods that can be utilized to study increasingly complex aspects of large scale protein-mediated membrane processes, and (2) the elaboration of the mechanisms by which key proteins target and remodel biological membranes. Three classes of protein-membrane systems will be studied: peripheral membrane proteins (the BAR domain family and how they remodel membranes), transmembrane proteins (influenza M2 protein and how it interacts with the membrane to generate membrane curvature in the course of viral budding), and signaling proteins (PKC, PDK1, and AKT1) to help elucidate the events that take place in the course of the membrane targeting and association by these proteins. The overarching long term goal of this research is to continue to develop and apply a powerful and systematic multiscale computational approach in the study of realistic protein-mediated membrane phenomena.