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

描述（由申请人提供）：该实验室开发了新的工艺质量管理方法，该方法使用全原子接触分析（包括氢）和更新的扭转角标准来指导改进蛋白质和核酸实验3D结构的程序。对一组15种晶体结构的初步研究已经在全原子碰撞、不良侧链旋转异构体、“翻转”Asn/Gln/His和Ramachandran异常值的平均得分方面实现了5到10倍的真正戏剧性改善，同时改善了与数据的拟合（晶体学Rfree通常下降1到3%）。RNA骨架和NMR结构的质量分数显示出严重但可能纠正的问题;就像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的X射线和NMR结构准确性的突破性改进。对于蛋白质晶体结构，这些技术将尽可能广泛地传播，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细化，并通过研究最佳局部骨架移位和更可行的表面侧链多种构象的结合来进一步增强。对于RNA和NMR结构，将完成一套适当的评价标准，并将开发和测试用于结构改进和细化的有效技术。NMR系综只有在实验数据需要的地方才有“离群”构象，而不是在数据不足以排除它们的地方。对于最好的X射线和NMR结构，内部已经相互吻合，并符合我们的质量标准;这里所追求的连接方法应该使它们的结果比现在更相似，即使是表面环和侧链。这种调和的有效性必须通过与实验数据更好的一致性来证明（对于X射线，更低的Rfree;对于NMR，更少的约束违反和更好地匹配新的附加类型的数据），并最终通过其他人的各种生物医学用途的结构的改进性能来证明。

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.