ITR: Subnanometer Structure Based Fold Determination of Biological Complexes

EIA-0325004-贝勒医学院华智合作者：基于亚纳米结构的生物复合体折叠测定。我们建议组成一个由三名具有不同专业知识的独立研究人员组成的团队，共同开发必要的计算和可视化方法，使生物学家能够快速、轻松和准确地推断大分子复合体的结构域组分的折叠。虽然大分子复合体的结构变得越来越普遍，一些密度图的大小将增加到1 GB，但提取重要生物信息的可视化和分析要求远远超出了目前可用的软件。我们的研究任务将探索不同的算法，通过对三维结构的去噪来增强信号，有效地可视化这些大的和过滤的地图，准确地提取单个蛋白质组分及其显著的结构特征，如a螺旋和b片层，并最终以蛋白质序列和结构考虑为约束，利用新的结构预测方法构建伪原子模型。我们将建立一个测试数据集，包括模拟和实验结构，以验证我们的每个开发步骤。每个研究站点的软件开发将使用脚本语言(Python)粘合在一起，并通过图形界面使其易于使用。此外，该软件将通过开放源码政策广泛记录和分发，鼓励继续合作和开发。

EIA-0325004 -Baylor College of Medicine Wah Chi COLLABORATIVES: ITR: Subnanometer Structure Based Fold Determination of Biological Complexes .We propose to form a team of three independent investigators with different expertises to co-develop the necessary computation and visualization methodology for biologists to quickly, easily and accurately deduce the folds of the domain components of large macromolecular complexes. While structures of macromolecular complexes are becoming more prevalent, and the size of some density maps would increase up to 1GB, the visualization and analysis requirements to extract important biological information are far beyond the currently available software. Our research task will explore different algorithms to enhance the signal through denoising of the 3-dimensional structure, visualize these large and filtered maps effectively, extract the individual protein components and their salient structural features such as a helices and b sheets accurately, and ultimately construct pseudo atomic model with novel structure prediction methods using protein sequence and structure considerations as constraints. We will set up a test data set, comprised of both simulated and experimental structures, to validate each of our development steps. The software developments in each of the research sites will be glued together using a scripting language (Python) and made easy to use through a graphical interface. Additionally, the software will be extensively documented and distributed via an open source policy, encouraging continued collaboration and development.