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

扩展 MolProbity 诊断

• 批准号: 10166392
• 负责人: DAVID Claude RICHARDSON
• 金额: $ 24.15万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166392
• 关键词: 20 year old; 3-Dimensional; Address; Biology; Code; Communication; Communities; Computer software; Contractor; Coupled; Cryoelectron Microscopy; Crystallography; Data; Deposition; Diagnosis; Drug Design; Future; Goals; Hand; Hydrogen; Hydrogen Bonding; Individual; Internet; Investments; Laboratories; Language; Libraries; Maintenance; Measures; Memory; Methods; Modeling; Modernization; Molecular Machines; Nucleic Acids; Occupations; Play; Process; Proteins; Pythons; RNA; Reading; Reporting; Research Project Grants; Resolution; Ribose; Roentgen Rays; Role; Secure; Security; Services; Software Tools; Software Validation; Standardization; Structural Biologist; Structure; System; Testing; Time; Update; Vaccines; Validation; Vertebral column; Work; Writing; base; conformer; data structure; data warehouse; design; experience; healing; improved; interest; interoperability; macromolecule; model building; open source; programs; software systems; structural biology; structured data; three-dimensional modeling; virtual machine; web services

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.

摘要/补充摘要 Molprobity大分子模型验证分配了总体质量得分，但最重要的是，它报告了 具有图形标志的可疑本地错误，可以帮助结构生物学家解决其中的大多数错误。这是 被认为是用于模型验证的最先进的，具有大量的全球用户群，已纳入大多数 模型构建和改进软件系统，对于蛋白质数据库中的模型验证至关重要。 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空间“冲突”≥0.4Å）。那 通过传统验证措施的更新版本来增强霉菌的独特特征 作为Ramachandran和Rotamers，带有RNA Ribose Pucker和Backbone构象异构体，最近 新标准（例如Cablam）在2.5-4Å分辨率上特别有用 令人兴奋的“分子机”通过晶体学或冷冻仪获得。 这种有效且使用广泛的工具集中的程序是潜水员，相当松散的耦合，有些是 20多年来。一段时间以来，他们非常需要深层改写和现代化 超越学术研究赠款可以支持，以保持维护，可扩展和健壮。 我们对霉菌代码的问题是这种新型补充剂旨在的困境 解决，为了提供开放的科学软件，使其用户能够充分利用广泛的优势 现在可以实现安全稳定的可访问性，互操作性和重复使用的功能。我们相信 Molprobity值得这项投资，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。 我很幸运地确定了一个在许多挑战中经验丰富的专业承包商 计算改进，重写和交互式3D图形，这有点熟悉 大分子和在进行该项目时有趣。当前的计划是统一我们的Molprobity代码 围绕Python的基础，呼叫C ++或C中的良好优化和硬化的库，并使用相同的库 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 与Phenix软件系统集成在一起的最新程序所使用的实用程序。这 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。