A New Method for Biomembrane Simulations

生物膜模拟的新方法

• 批准号: 8073279
• 负责人: Gregory A. Voth
• 金额: $ 16.58万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8073279
• 关键词: New; Method; Biomembrane; Simulations; New; Method; Biomembrane; Simulations

DESCRIPTION (provided by applicant): This competing renewal application is devoted to the continued development and application of a unique and powerful multiscale computational approach to describe membranes and membrane processes. The project involves the rigorous bridging of scales using a "bottom-up" approach that is capable of translating molecular scale behavior into emergent mesoscopic scale phenomena. Extensive atomistic molecular dynamics simulations, along with novel enhanced sampling methods, are utilized to systematically develop powerful and thermodynamically consistent multiscale coarse-grained (MS-CG) models at the desired level of resolution. The MS-CG approach, which was a key breakthrough during the last funding period and is several orders of magnitude more computationally efficient than all-atom simulations, is in turn used to systematically construct mesoscopic simulation models in a multiscale fashion. The latter models allow for even larger length and time scale membrane phenomena to be accurately simulated. The Specific Aims of this project are: (Aim 1) the continued development of the transformative multiscale simulation methodology for the description of realistic heterogeneous membranes and membrane bound proteins, with a goal of making computer simulation more directly relevant to the fluid mosaic picture of real biological membranes; (Aim 2) the application of the multiscale simulation methodology to large scale membrane remodeling phenomena, driven by BAR domain and ENTH domain protein modules, in close collaboration with experimentalists; and (Aim 3) the application of mixed resolution all-atom/coarse-grained simulation methods to the membrane binding and aggregation of the matrix domain (MA) of the HIV-1 Gag polyprotein and the mechanosensitive channel of large conductance (MscL), again in collaboration and close contact with experimental research. The overarching long term goal of this project is to develop and apply a powerful, systematic, and rigorous multiscale computational approach to the study of biologically realistic membranes and membrane protein associated phenomena. PUBLIC HEALTH RELEVANCE: Statement The project concerns the development and application of novel multiscale computer simulation methods for biomembrane systems. The target systems to be studied play a role in rare neurologic autoimmune disease, paraneoplastic Stiff-Man syndrome with breast cancer, Alzheimer's disease, Huntington's disease, pyogenic arthritis, influenza virus entry, the physiological basis for hearing, proprioception, and osmotic regulation, and the late stage of HIV-1 virus replication.

描述（由申请人提供）：此竞争续约应用程序致力于持续开发和应用独特而强大的多尺度计算方法来描述膜和膜过程。该项目涉及使用“自下而上”的方法对量表进行严格的桥接，该方法能够将分子尺度行为转化为新兴的介观量表现象。广泛的原子分子动力学模拟以及新型增强的采样方法可在所需的分辨率水平上系统地开发出强大的热力学一致性粗粒（MS-CG）模型。 MS-CG方法是在上一个融资期间的关键突破，并且比所有原子模拟的计算效率高几个数量级，又用于系统地以多尺度方式构建中镜模拟模型。后一个模型允许精确模拟更大的长度和时间尺度现象。该项目的具体目的是：（目标1）持续开发变革性的多尺度仿真方法，以描述现实的异质膜和膜结合蛋白质，目的是使计算机模拟与真实生物膜的流体镶嵌图更直接相关； （AIM 2）与实验者密切合作，将多尺度仿真方法应用于大规模膜重塑现象，由条形域和Enth域蛋白模块驱动； （AIM 3）混合分辨率全原子/粗粒仿真方法应用于HIV-1 GAG多蛋白的矩阵结构域（MA）的膜结合和聚集，并在协作和与实验研究的协作中再次接触大型电导（MSCL）的机械敏感通道（MSCL）。该项目的总体长期目标是开发和应用强大的，系统的，严格的多尺度计算方法来研究生物学上现实的膜和膜蛋白相关现象。 公共卫生相关性：声明该项目涉及生物膜系统的新型多尺度计算机模拟方法的开发和应用。要研究的目标系统在罕见的神经系统自身免疫性疾病，副塑性僵硬症综合征与乳腺癌，阿尔茨海默氏病，亨廷顿病，亨廷顿氏病，化脓性关节炎，流感病毒的进入，助听器的生理基础，助听器，本体感受，渗透调节和渗透调节调节以及Hiv-1 niv-1 niv-1 Virecation。