Molecular Modeling

三. TR&D1 -摘要 在过去的十年中，4D建模方法的创新性非常强 生物分子系统，使用粗粒度模型和增强采样方法，以及 在细胞尺度上的时空现实方法。然而，“中尺度”系统，如大型 多蛋白质复合物和亚细胞结构，以及“组学规模”的系统，如染色质， 受到的关注明显较少。有一个激增的需要，发展计算技术， 基于结构的介观和空间分辨omics尺度建模。几种方法 TR&D1研究人员已经开发出了满足这一需求的巨大希望。这些包括 基于弹性网络模型的方法和工具，并在ProDy中实现 应用程序编程接口（API）开发用于建模超分子系统动力学， 以及为鉴定染色体中拓扑相关结构域而开发的Armatus软件。 我们的目标是进一步发展这些和其他创新技术，我们在开发期间， 过去的任期，如加权集成（WE）为基础的方法和软件（WESTPA），以提高 模拟效率适用于分子和细胞尺度，对解决这些新的 新出现的挑战。我们的研发活动将由四个驱动生物医学 项目将集中在控制神经传递和神经信号的复杂相互作用 事件（DBP 1 -3），以及构建转录和染色质结构的空间动态图 （DBP6）。我们将与所有其他三个TR& D合作，以满足多尺度的挑战， 研究复杂的系统和过程。我们的目标是：（1）推进和 实施用于处理多聚体的结构、动力学和相互作用的方法， 蛋白质和多蛋白质组装，（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;（3）进一步开发TR&D1高表达基因。 PSC提供的Bridges环境下的高性能计算（HPC）平台，以确保 TR&D1中所有软件的有效集成，以及与在 其他三个TR& D，以及其他追求互补目标的资源。

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.