New Kind of Quality Management for X-ray and NMR Models

X 射线和 NMR 模型的新型质量管理

• 批准号: 7921709
• 负责人: DAVID Claude RICHARDSON
• 金额: $ 4.93万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921709
• 关键词: Agreement; Coupled; DNA; Data; Databases; Diagnosis; Disease; Docking; Effectiveness; Evaluation; Glutamine; Hydrogen; Laboratories; Libraries; Link; Measurement; Membrane Proteins; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Motion; Nucleic Acids; Performance; Positioning Attribute; Procedures; Process; Proteins; RNA; Research; Research Personnel; Resolution; Roentgen Rays; Side; Source; Staging; Structural Biologist; Structure; Surface; Techniques; Testing; Time; Torsion; Update; Vertebral column; Work; falls; improved; member; model design; nucleic acid structure; programs; sound; three dimensional structure; tool

DESCRIPTION (provided by applicant): This laboratory has developed new process quality management methods that use all-atom contact analysis (including the hydrogens) and updated torsion-angle criteria to guide procedures for improving experimental 3D structures of proteins and nucleic acids. Preliminary studies on a set of 15 crystal structures have achieved a truly dramatic improvement by factors of 5 to 10 in the average scores for all-atom clashes, poor sidechain rotamers, "flipped" Asn/Gln/His, and Ramachandran outliers, while at the same time improving fit to the data (crystallographic Rfree down by typically 1 to 3%). Quality scores on RNA backbone and on NMR structures show serious but potentially correctable problems; as in protein crystal structures, even the most careful structural biologists did not previously have the independent information added by these new methods. This project, therefore, aims to achieve the benefits of breakthrough improvements in accuracy for both x-ray and NMR structures of both proteins and nucleic acids. For protein crystal structures, these techniques will be disseminated as widely as possible, applied to the correction and re-refinement of specific structures critical either for biomedical importance or for theoretical calculations, and enhanced further by researching optimal local backbone shifts and more feasible incorporation of multiple conformations of surface side chains. For RNAs and for NMR structures, the suitable set of evaluation criteria will be completed and effective techniques for their use in structure improvements and refinement will be developed and tested. The NMR ensembles will have "outlier" conformations only where the experimental data requires them, rather than where the data is insufficient to rule them out. For the very best x-ray and NMR structures, the interiors already agree well with each other and with our quality criteria; the connected approaches being pursued here should make their results much more similar than at present, even for surface loops and sidechains. The validity of such a reconciliation must be proven by better agreement with experimental data (for x-ray, lower Rfree; for NMR, fewer constraint violations and better match to new additional types of data) and ultimately by improved performance of the structures for various biomedical uses by others.

描述（由申请人提供）：该实验室开发了新的过程质量管理方法，使用全原子接触分析（包括氢）和更新的扭转角度标准，以指导改进蛋白质和核酸的实验3D结构的程序。对一组15个晶体结构的初步研究在全原子冲突的平均得分，较差的Sidechain Rotamers的平均得分中取得了真正的巨大改善，“翻转” ASN/GLN/HIS和Ramachandran Outliers，同时通过数据（Crystallographics fialoprical fialosection fialopricationallography potheragraphics contallographics fit fialosectionallograpen）（典型地降低了典型的典型）。 RNA主链和NMR结构上的质量得分显示出严重但可能正确的问题；与蛋白质晶体结构一样，即使是最仔细的结构生物学家，以前也没有这些新方法添加的独立信息。因此，该项目旨在实现蛋白质和核酸X射线和NMR结构的突破性改善的好处。对于蛋白质晶体结构，将尽可能广泛地传播这些技术，应用于对生物医学重要性或理论计算至关重要的特定结构的校正和重新启动，并通过研究最佳的局部骨架移位和更可行的表面侧面链链多种构象来进一步增强。对于RNA和NMR结构，将完成一组合适的评估标准，并将开发和测试其在结构改进和改进中的有效技术。 NMR合奏只有在实验数据需要的情况下才具有“离群”构象，而不是数据不足以排除它们的位置。对于最好的X射线和NMR结构，内饰已经彼此同意，并且与我们的质量标准一致。在这里采用的连接方法应该使其结果比目前更相似，即使对于表面环和侧层也是如此。必须通过与实验数据更好地一致（对于X射线，较低的RFRE；对于NMR，更少的约束违规，与新的其他类型的数据匹配），并最终通过改善其他人的生物医学用途的结构性能改善结构的性能。