Molecular Modeling

分子模拟

• 批准号: 10228747
• 负责人: Ivet Bahar
• 金额: $ 41.62万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228747
• 关键词: Address; Algorithms; Amino Acid Transporter; Attention; Automation; Automobile Driving; Benchmarking; Biomedical Research; Cell Adhesion Molecules; Cellular Structures; Cellular biology; Chromatin; Chromatin Structure; Chromosome Structures; Chromosomes; Collaborations; Communities; Complex; Computer software; Computing Methodologies; Data; Databases; Development; Ensure; Environment; Event; Excitatory Amino Acids; Funding; Genetic Transcription; Goals; Grain; Graph; High Performance Computing; Image; Ions; Ligands; Lipids; Machine Learning; Maps; Measurement; Measures; Methodology; Methods; Modeling; Molecular; Multiprotein Complexes; Plant Roots; Process; Protein Subunits; Proteins; Protocols documentation; Publications; Research Personnel; Resources; Sampling; Scaffolding Protein; Statistical Mechanics; Structure; Subcellular structure; Synapses; System; Techniques; Technology; Time; Vision; Work; application programming interface; base; biological systems; chromosome conformation capture; computational platform; computing resources; conformational conversion; dopamine transporter; experience; genome analysis; genome sciences; genome-wide; genomic locus; innovative technologies; interoperability; invention; meetings; member; molecular modeling; multi-scale modeling; network models; neurotransmission; novel; postsynaptic; research and development; simulation; software development; spatiotemporal; theories; tool; user-friendly

III. TR&D1 - Abstract The last decade has seen the creation of a remarkably inventive array of approaches for 4D modeling of biomolecular systems, using coarse-grained models and enhanced-sampling methods, as well as spatiotemporally realistic approaches at cellular scale. However, “mesoscale” systems such as large multi-protein complexes and subcellular structures, and “omics-scale” systems like chromatin have received significantly less attention. There is a surging need to develop computational technology for structure-based mesoscopic- and spatially resolved omics-scale modeling. Several methodologies already developed by TR&D1 investigators show great promise for meeting this need. These include the methods and tools based on elastic network models (ENMs) and implemented in the ProDy Application Programming Interface (API) developed for modeling supramolecular systems dynamics, and the Armatus software developed for identifying topological associated domains in chromosomes. Our goal is to further develop these and other innovative technologies that we developed during the past term, such as weighted-ensemble (WE)-based methods and software (WESTPA) for enhancing simulation efficiency applicable to both molecular and cellular scales, toward addressing these newly emerging challenges. Our research and development activities will be driven by four Driving Biomedical Projects that will focus on the complex interactions controlling neurotransmission and neurosignaling events (DBP1-3), and on constructing a spatial dynamic map of transcription and chromatin structure (DBP6). We will work together with all three other TR&Ds to meet the multiscale challenges of the investigated complex systems and processes. Our aims are formulated as (1) advancing and implementing the methodology for treating the structure, dynamics, and interactions of multimeric proteins and multiprotein assemblies, (2) extending our computing capabilities to modeling chromosomal structure, dynamics and function, and (3) further development of TR&D1 high- performance computing (HPC) platform under the Bridges environment provided by the PSC, to ensure efficient integration of all software within TR&D1, as well as interoperability with those developed at the other three TR&Ds, and at other Resources pursuing complementary goals.

iii。 TR＆D1-摘要 在过去的十年中，创造了4D建模的一种非常发明的方法 使用粗粒模型和增强抽样方法的生物分子系统以及 在细胞尺度上采用时空现实的方法。但是，“中尺度”系统，例如大型 多蛋白质络合物和亚细胞结构，以及像染色质这样的“ OMICS规模”系统具有 受到明显的关注。有急需开发计算技术的 基于结构的介观和空间分辨的法尺度建模。几种方法 TR＆D1调查人员已经开发了满足这一需求的巨大希望。这些包括 基于弹性网络模型（ENM）的方法和工具，并在Prody中实现 为建模超分子系统动力学而开发的应用程序编程接口（API）， Armatus软件开发了用于识别染色体中拓扑相关的域。 我们的目标是进一步开发我们在我们期间开发的这些创新技术 上学期，例如加权 - 基于（我们）的方法和软件（Westpa） 适用于分子和细胞尺度的仿真效率，用于解决这些新的 新兴挑战。我们的研发活动将由四个驾驶生物医学驱动 将重点关注控制神经传递和神经信号的复杂互动的项目 事件（DBP1-3），以及构建转录和染色质结构的空间动态图 （DBP6）。我们将与其他三个TR＆D一起工作，以应对 研究了复杂的系统和过程。我们的目标被提出为（1）前进和 实施处理多聚体的结构，动力学和相互作用的方法 蛋白质和多蛋白质组件，（2）将我们的计算能力扩展到建模 染色体结构，动力学和功能，以及（3）TR＆D1的进一步发展 PSC提供的桥梁环境下的性能计算（HPC）平台，以确保 有效地集成了TR＆D1中的所有软件，以及与在 其他三个TR＆D，以及其他资源实现完整目标。