WHOLE CELL SIMULATION

全细胞模拟

• 批准号: 10163206
• 负责人: Klaus Schulten
• 金额: $ 61.73万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2022-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163206
• 关键词: Address; Advanced Development; Area; Base Composition; Behavior; Binding; Bioinformatics; Biological; Cell Death; Cell membrane; Cell model; Cell physiology; Cells; Cellular Membrane; Cellular Structures; Cellular biology; Chemicals; Code; Complex; Computer software; Computing Methodologies; Crowding; Cryo-electron tomography; Cryoelectron Microscopy; Crystallography; DNA; DNA Structure; Data; Data Analyses; Development; Diffusion; Disease; Endoplasmic Reticulum; Equation; Equilibrium; Eukaryotic Cell; Evolution; Future; Goals; Hour; Hybrids; Image; Length; Life; Link; Lipids; Membrane; Membrane Proteins; Messenger RNA; Methodology; Methods; Microbe; Mitochondria; Modeling; Modernization; Molecular; Molecular Biology; Motion; Organelles; Organism; Pharmaceutical Preparations; Positioning Attribute; Probability; Process; Proteins; Reaction; Research Personnel; Resolution; Ribosomes; Shapes; Signal Transduction; Software Tools; Source; Speed; Structural Models; Structure; Subcellular structure; System; Systems Biology; Techniques; Technology; Testing; Time; Visualization; Work; X-Ray Crystallography; advanced simulation; base; cell behavior; cell community; chemical reaction; computerized tools; data modeling; density; experimental study; flexibility; macromolecular assembly; macromolecule; membrane model; metaplastic cell transformation; millisecond; model building; model design; model development; models and simulation; molecular dynamics; molecular scale; multimodal data; network models; next generation; novel; parallel computer; particle; simulation; structural biology; support tools; tomography; tool

Project Summary / Abstract The living cell represents a spatially complex and highly regulated arrangement of molecules whose coordinated motions and activities underlie all the processes within the cells allowing them to grow, reproduce, and carry out a wide spectrum of diverse cellular functions. Along with an increasing number of experimental techniques targeting the identification of the position of subcellular organelles, ribosomes, and macromolecules such as proteins, mRNA, and DNA, there is a growing demand for the next generation of computational tools that allow researchers to construct realistic, cellular-scale structural models at a range of resolutions, to resolve molecular functional states, and to simulate their stochastic, time-dependent behavior in both healthy and diseased cells. The Whole Cell Simulation TRD (TRD3) focuses on a number of software and methodological developments that seek to enable the modeling and simulation of cellular-scale systems. The Center will develop and extend software tools in four complementary modeling areas in cell biology that cover several orders of magnitude in length and time scales: The Molecular Dynamics Flexible Fitting (MDFF) tool enables structural modeling and analysis of large macromolecular assemblies in various functional states through the use of multimodal data, including cryo-electron microscopy (cryo-EM). The future focus of MDFF resides in incorporating advanced simulation methods in an automated fashion to overcome the challenges posed by complex molecular systems, particularly those involving the increasingly obtainable high-resolution cryo-EM data. The Cellular Membrane Modeling (CMM) tools will facilitate model building, simulation, and analysis of com- plex, cellular-scale membrane structures and processes. Technical development will focus on methods and software for constructing realistic membrane models of cells and cellular organelles ( e.g., mitochondria or endoplasmic retic- ulum) with realistic lipid/protein compositions based on experimental data, efficient embedding of proteins into membrane models, and dynamic reshaping of membrane structures during simulation. The Atomic Resolution Brownian Dynamics (ARBD) tools support simulations of micrometer-scale systems of interacting biomolecules (e.g., the binding of a drug to a ribosome or a signalling cascade leading to cell death) at millisecond and greater time scales. Future work will focus on leveraging GPU technology to speed up simulations, developing tools to construct, visualize, and share BD models, and methods for incorporating chemical reactivity into BD simulations. The GPU-based Lattice Microbes (LM) suite of systems biology simulation tools integrates data from super- resolution imaging, cryo-electron tomography, and -omics experiments into stochastic simulations of reaction diffusion processes in bacterial and eukaryotic cells and colonies over biologically relevant time (hours) and length (µm to mm) scales. Future developments will increase the size and complexity of the models LM can simulate, and facilitate the incorporation of more diverse sets of experimental data during model design and analysis.

项目摘要 /摘要 活细胞代表了分子的空间复杂且高度规范的排列，其协调 与细胞一起允许它们成长的所有过程的动作和活动，并执行 各种各样的细胞功能以及越来越多的实验技术 亚细胞细胞器，核糖体和大分子（例如蛋白质，mRNA，mRNA）的位置的鉴定。 和DNA，对下一个计算工具工具工具工具工具的需求越来越大。 在各种分辨率上构建现实的细胞尺度结构模型，以解决分子功能状态， 并在健康细胞和患病细胞中模拟它们的随机行为 仿真TRD（TRD3）重点介绍许多旨在启用的软件和方法论的开发 蜂窝尺度系统的建模和模拟。 细胞生物学中的编译区域涵盖长度和时间尺度的数量级。 分子动力学柔性拟合（MDFF）工具可以实现大型结构建模和分析 各种功能状态中的大分子组件使用多模式数据，包括冷冻电子 显微镜（Cryo-EM）。 自动化时尚，以克服复杂分子系统所面临的挑战，尤其是涉及的挑战 越来越可获得的高分辨率冷冻。 细胞膜建模（CMM）工具将促进模型建设，模拟和分析 PLEX，细胞尺度的膜结构和过程。 用于构建细胞和细胞细胞器的逼真的膜模型（例如，线粒体或内质网 ulum）基于实验数据，具有逼真的脂质/蛋白质成分，将蛋白质嵌入到 膜模型和模拟过程中膜结构的动态重塑。 原子分辨率布朗动力学（ARBD）工具支持千分表规模系统的模拟 在相互作用的生物分子（例如，药物与核糖体或信号级联导致细胞死亡的结合） 毫秒和更大的时间尺度。 开发用于构建，可视化和共享BD模型的工具，以及结合化学反应性的方法 进入BD模拟。 基于GPU的晶格微生物（LM）系统生物学模拟工具套件整合了超级数据的数据 分辨率成像，冷冻电子断层扫描和 - 摩学实验，以实现现实的随机性 在生物学上相关的时间（小时）和长期三分之二的细菌和真核细胞和菌落中的分解过程 （µm至mm）尺度。 并促进了更多种实验数据设计和分析集合集合。