New Method for Biomembrane Simulations

描述（由申请人提供）：本次更新申请的重点是持续开发和应用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尺度（即连续体尺度、介观尺度和原子尺度）的三个相互关联的体系开发概念和计算方法。一般来说，这三种制度在其相关长度和时间尺度上最多相差三个数量级。在该项目中，将继续为这三种体系（特别是在具有挑战性的连续体和介观尺度上）开发新方法，重要的是，它们将以多尺度计算方式连接在一起。由此产生的具体目标将涉及：(1) 开发多尺度模拟方法，用于描述膜结合蛋白和肽，具体应用于响应外部施加压力而门控的机械敏感通道、被认为会引起膜弯曲的含 BAR 结构域的蛋白，以及影响离子通道功能的神经活性肽； （2）介观模拟组件与核磁共振测量的耦合，以验证下一代介观模型并揭示复杂的、实验观察到的介观和原子级膜运动的起源； （3）通过场论与计算连续介质力学的新颖综合，开发与大规模膜运动和变形耦合的脂质域形成和动力学的连续介质级描述。该项目的总体长期目标是为生物学上重要的膜和膜结合过程的计算研究提供一种新的多尺度、基于物理的方法。

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.