New Method for Biomembrane Simulations

生物膜模拟的新方法

• 批准号: 6976854
• 负责人: Gregory A. Voth
• 金额: $ 28.41万
• 依托单位: UNIVERSITY OF UTAH
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6976854
• 关键词: artificial membranes; cell membrane; computational biology; computer simulation; lipid bilayer membrane; membrane activity; membrane channels; membrane model; membrane proteins; membrane structure; molecular dynamics; nanotechnology; structural biology

DESCRIPTION (provided by applicant): The focus of this renewal application is the continued development and application of a unique multiscale approach to study membranes and membrane-bound processes. The project involves the development of conceptual and computational methodologies for three interconnected regimes at three different scales, i.e., the continuum, mesoscopic, and atomistic scales. Generally speaking, these three regimes are separated by up to three orders-of-magnitude in their relevant length- and time-scales. In this project, new approaches will continue to be developed for each of the three regimes (especially at the challenging continuum and mesoscopic scales) and, importantly, they will be linked together in a multi-scale computational fashion. The resulting Specific Aims will involve: (1) the development of a multi-scale simulation approach for the description of membrane bound proteins and peptides, with specific applications to mechanosensitive channels that are gated in response to external applied stress, BAR domain-containing proteins which are believed to induce membrane curvature, and neuroactive peptides that affect ion channel function; (2) the coupling of the mesoscopic simulation component to NMR measurements in order to both validate the next generation mesoscopic model and to unravel the origins of complex, experimentally observed mesoscopic and atomistic-level membrane motions; and (3) the development of a continuum-level description of lipid domain formation and dynamics coupled to large-scale membrane motion and deformation, through a novel synthesis of field theory with computational continuum mechanics. The overarching long term goal of this project is to provide a new multi-scale, physics-based approach for the computational study of biologically important membrane and membrane-bound processes.

描述（由申请人提供）：本次更新申请的重点是继续开发和应用一种独特的多尺度方法来研究膜和膜结合过程。该项目涉及为三个不同规模的三个相互关联的制度制定概念和计算方法，连续体、介观和原子尺度。一般而言，这三种制度在其相关的长度和时间尺度上被多达三个数量级分开。在该项目中，将继续为三种机制中的每一种机制开发新的方法（特别是在具有挑战性的连续体和介观尺度上），重要的是，它们将以多尺度计算方式联系在一起。由此产生的具体目标将包括：（1）开发用于描述膜结合蛋白质和肽的多尺度模拟方法，具体应用于响应于外部施加的应力而门控的机械敏感性通道、被认为诱导膜弯曲的含有BAR结构域的蛋白质以及影响离子通道功能的神经活性肽;（2）介观模拟组件与NMR测量的耦合，以便验证下一代介观模型并解开复杂的、实验观察到的介观和原子级膜运动的起源;以及（3）发展了与大尺度膜运动和变形相耦合的脂质结构域形成和动力学的连续水平描述，通过场论与计算连续介质力学的新综合。该项目的总体长期目标是为生物重要的膜和膜结合过程的计算研究提供一种新的多尺度，基于物理学的方法。