Extending MolProbity Diagnosis & Healing Methods to Empower Better CryoEM & Xray Models at 2.5-4A Resolution, plus Versioned, Redeposited "GEMS" for Important Individual Structures

附录摘要/摘要 MolProbity大分子模型验证为整体质量评分，但最重要的是，它报告 可能的局部错误，带有帮助结构生物学家修复大多数错误的图形标志。它是 被认为是最先进的模型验证，在全球拥有庞大的用户基础，被整合到大多数 模型建立和改进软件系统，是蛋白质数据库模型验证的核心。 组件程序添加和优化氢原子，以分析和显示全原子接触(H- 债券，有利的范德华，和严重的立体“冲突”的不利重叠≥0.4o)。那 MolProbity的独特功能通过传统验证方法的更新版本进行了增强，例如 作为Ramachandran和旋转异构体，具有RNA核糖折叠和主干构象，以及最近的 新的标准，如CaBLAM，在2.5-4？分辨率上特别有用，用于 由结晶学或低温电子显微镜获得的激动人心的“分子机器”。 这个有效且广泛使用的工具集中的程序是多样的，而且是相当松散耦合的，有些是 已经20多岁了。很长一段时间以来，他们一直非常需要深度改写和现代化 超出学术研究拨款所能支持的范围，以保持可维护性、可扩展性和健壮性。 我们对MolProbity代码的问题是这种新型补充设计的那种两难境地 解决方案，以便提供开放的科学软件，使其用户能够充分利用 现在有可能实现安全稳定的可访问性、互操作性和重用。我们相信 MolProbity值得这笔投资，首先是结构生物学社区，其次是生物医学 这些结构的最终用户。 我非常幸运地找到了一位在许多挑战方面经验丰富的专业承包商 计算改进、重写和交互式3D图形，对 大分子，并有兴趣承担这个项目。目前的计划是统一我们的MolProbity代码 通过调用C++或C++中经过良好优化和强化的库来基于Python，并使用相同的 标准格式解析器、内部数据层次结构、内存通信和打开CCTBX工具箱 我们与Phenix软件系统集成的最新程序所使用的实用程序。这个 重写将包括更完整的回归测试，开发标准化的构建过程，并探索 Web服务的各种云托管选项。

Summary/Abstract for Supplement MolProbity macromolecular model validation assigns overall quality scores, but most importantly, it reports probable local errors with graphic flags that help structural biologists fix most of those errors. It is considered state-of-the-art for model validation, has a large worldwide user base, is incorporated into most model-building and refinement software systems, and is central to model validation at the Protein DataBank. The component programs add and optimize hydrogen atoms to analyze and display all-atom contacts (H- bonds, favorable van der Waals, and serious steric "clashes" of unfavorable overlaps ≥0.4Å). That distinctive feature of MolProbity is augmented with updated versions of traditional validation measures such as Ramachandran and rotamers, with RNA ribose pucker and backbone conformers, and most recently with new criteria such as CaBLAM that are especially useful at the 2.5-4Å resolutions common for structures of exciting "molecular machines" obtained by crystallography or cryoEM. The programs in this effective and widely used toolset are diverse and rather loosely coupled, and some are more than 20 years old. For quite a while they have been in great need of a deep rewrite and modernization beyond what an academic research grant can support, in order to stay maintainable, extensible, and robust. Our problem with the MolProbity code is the sort of dilemma that this new type of supplement is designed to solve, in order to provide open scientific software that enables its users to take full advantage of the broad capabilities now possible for secure and stable accessibility, interoperability, and re-use.We believe MolProbity is worth this investment, first to the structural biology community and second to the biomedical end-users of these structures. I am very fortunate to have identified a professional contractor highly experienced in many challenging computational improvements, rewrites, and interactive 3D graphics, that is somewhat familiar with macromolecules and interested in taking on this project. The current plan is to unify our MolProbity code base around Python with calls to well-optimized and hardened libraries in C++ or C, and to use the same standard-format parsers, internal data hierarchy, in-memory communication, and open CCTBX toolbox utilities used by the most recent of our programs which are integrated with the Phenix software system. The rewrite will include more complete regression tests, develop a standardized build process, and explore a variety of cloud hosting options for the web service.