Molecular Modeling

三、tr&d1-摘要 在过去的十年里，人们创造了一系列非常有创意的4D建模方法 生物分子系统，使用粗粒度模型和增强采样方法，以及 细胞尺度上的时空现实方法。然而，“中尺度”系统，如大型 多蛋白质复合体和亚细胞结构，以及像染色质这样的“组学规模”系统 受到的关注明显减少。开发计算机技术的需求激增，以 基于结构的介观和空间分辨组学尺度建模。几种方法 研究人员已经开发出了满足这一需求的大有希望。这些措施包括 基于弹性网络模型的方法和工具及其在产品中的实现 为模拟超分子系统动力学而开发的应用编程接口(API)， 以及Armatus软件，用于识别染色体中的拓扑相关结构域。 我们的目标是进一步开发这些技术和我们在 过去，例如基于加权集成(WE)的方法和软件(WESTPA)，用于增强 适用于分子和细胞尺度的模拟效率，以解决这些新的 新出现的挑战。我们的研究和开发活动将由四个驱动生物医学 将专注于控制神经传递和神经信号传递的复杂相互作用的项目 事件(DBP1-3)，以及构建转录和染色质结构的空间动态图 (DBP6)。我们会与其他三个研发及发展署携手合作，迎接 研究了复杂的系统和过程。我们的目标是：(1)推进和 实施处理多聚体的结构、动力学和相互作用的方法学 蛋白质和多蛋白质组合，(2)将我们的计算能力扩展到建模 染色体的结构、动力学和功能，以及(3)进一步发展的T_R&D_1高亲和性。 PSC提供的桥接环境下的性能计算(HPC)平台，以确保 有效集成tr&d1内的所有软件，并与在 其他三个研发项目，以及追求互补目标的其他资源。

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.