A New Method for Biomembrane Simulations

生物膜模拟的新方法

• 批准号: 9233676
• 负责人: Gregory A. Voth
• 金额: $ 32.45万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9233676
• 关键词: AKT1 gene; Alzheimer' s Disease; Area; Behavior; Binding; Binding Proteins; Biological; Biophysics; Cell division; Cells; Centronuclear myopathy; Cereals; Collaborations; Collection; Complex; Computer Simulation; Computing Methodologies; Coupled; Couples; Development; Dynamin; Electron Microscopy; Endocytosis; Event; Family; Funding; Future; Goals; Grant; Immune response; Infection; Influenza; Influenza A virus; Integral Membrane Protein; Length; Letters; Lipid Bilayers; Lipids; M2 protein; Malignant Neoplasms; Mediating; Membrane; Membrane Proteins; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Molecular Models; Morphology; Motion; Movement; Optics; Organelles; PDPK1 gene; Paper; Paris, France; Pathway interactions; Peripheral; Process; Proteins; Publishing; Research; Sampling; Signal Transduction; Signaling Protein; Stiff-Person Syndrome; Structure; System; Time; United States National Institutes of Health; Viral; Work; amphiphysin; cancer cell; cell motility; healing; influenzavirus; innovation; macromolecular assembly; malignant breast neoplasm; models and simulation; molecular dynamics; molecular modeling; molecular scale; multi-scale modeling; novel; protein complex; protein protein interaction; simulation; trafficking

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.

项目概要 膜靶向和重塑与许多关键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、信号传导和 移动。这些过程本质上是多尺度的，因为它们涵盖从分子到纳米级再到纳米级 介观时间和长度尺度。例如，集合之间的分子水平相互作用 蛋白质和脂质双层可以对大规模膜形态产生深远影响。主要 该项目的科学前提是，以跨多个尺度的耦合方式研究至关重要 局部分子相互作用在尺度上向上传播到集体和突发行为 介观水平。因此，该项目涉及新颖的技术的持续开发和应用 非常适合研究蛋白质集体相互作用的多尺度计算方法 与膜。 这项研究有两个主要组成部分：（1）开发新的多尺度模拟 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）详细阐述关键蛋白质靶向和重塑生物的机制 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 它如何与膜相互作用，在病毒出芽过程中产生膜曲率），以及 信号蛋白（PKC、PDK1 和 AKT1）有助于阐明在过程中发生的事件 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且系统的多尺度计算方法来研究 真实的蛋白质介导的膜现象。