MolProbity Service and Related 3D-Analysis Resources

描述(由申请人提供)：该项目将大大扩展和改进MOLPROBITY网络服务，用于分析、验证和改进3D大分子结构。它将增强MolPROBITY及其支持软件套件的基本能力、用户友好性、通用性、健壮性、可维护性和可扩展性，以使许多现有用户(今年的11,500次工作会议)以及更广泛的生物医学研究人员社区受益，他们现在希望使用它。MOLPROBITY有两个独特的功能来实现这些目标。1是带有显式氢原子的全原子接触分析，它以前所未有的详细程度显示了立体接触，并已被证明能够诊断和纠正实验结构模型中的大多数错误。第二个是在法师和国王中实现的运动图像概念，强调互动性和对3D关系的清晰感知。这个开源、跨平台的软件家族自1992年发展起来，支持结构生物学、生物化学、生物信息学、教育甚至非分子用途。新的蛋白质数据库网站和数据存储利用了这些验证和图形工具。大多数结构基因组学中心已经采用了MOLPROBITY，但希望进一步调整它以满足其生产线的需求。这个项目将支持开发和文档，这在纯研究工作中很难证明是合理的，但作为一个开放资源，它对于长期生存和增长是必不可少的。将增加对结构比较、MMCIF文件以及核磁共振系综和核酸分析的支持。程序将进行重新组织，以实现模块化，并更好地记录以供重复使用。MOLPROBITY的网络界面将进行修改，为评估沉积结构提供直观的简单性，并为结构生物学专家客户解决新结构提供强大的灵活性。来自其他网站的预先计算的数据库和链接将允许快速访问结构质量评估和比较，为更广泛的生物医学研究人员提供服务。命令行和Web服务界面将为分析数千个文件的新预测和生物信息学用户提供服务。用户/合作者的反馈、我们计算机科学合作研究员的建议，以及我们自己在研究使用该系统方面的经验将指导这一软件开发过程。对于公众健康，MOLPROBITY可以帮助新药的计算设计取得成功，特别是在时间有限的情况下(例如对抗SARS)，因为它帮助用户快速评估和提高通过实验确定的药物靶标模型的准确性。这里提出的工作将导致3D大分子数据库总体精度的显著提高，许多生物医学研究都依赖于3D大分子数据库。这对于与医学相关的“热门”结构尤其重要，因为时间压力目前会影响许多此类与健康相关的病例的质量。

DESCRIPTION (provided by applicant): This project will substantially extend and improve the MOLPROBITY web service for analyzing, validating, and improving 3D macromolecular structures. It will enhance the basic capabilities, user-friendliness, generality, robustness, maintainability, and extensibility of MolPROBITY and its suite of supporting software in order to benefit both the many current users (11,500 working sessions this year) as well as the even broader community of biomedical researchers who now wish to employ it. MOLPROBITY has 2 unique features that enable these goals. 1 is all-atom contact analysis with explicit hydrogens, which shows steric contacts in unprecedented detail and has been proven capable of diagnosing and correcting most errors in experimental structural models. The second is the kinemage graphics concept implemented in MAGE and KING, emphasizing interactivity and clear perception of 3D relationships. Growing since 1992, this open-source, cross-platform software family supports structural biology, biochemistry, bioinformatics, educational, and even non-molecular uses. The new Protein Data Bank website and data-deposition makes use of these validation and graphics tools. Most structural genomics centers have adopted MOLPROBITY, but want it further tuned to the needs of their production pipelines. This project will enable development and documentation that is hard to justify in a pure research effort but is essential for long-term viability and growth as an open resource. Support will be added for structure comparisons, mmCIF files, and analysis of NMR ensembles and nucleic acids. Programs will be reorganized for modularity and better documented for re-use. MOLPROBITY'S web interface will be revised to give both intuitive simplicity for evaluation of deposited structures and also powerful flexibility for expert structural-biology clients solving new ones. Precalculated databases and links from other websites will allow quick access to structure quality evaluations and comparisons, serving an even broader set of biomedical researchers. Command-line and web service interfaces will serve new prediction and bioinformatics users analyzing thousands of files. User/collaborator feedback, advice from our computer science co-investigator, and our own experience in research use of the system will guide this software development process. For public health, MOLPROBITY can aid the success of computational design of new drugs, especially under time constraint (e.g. against SARS), since it helps users rapidly assess and improve the accuracy of experimentally determined models of drug targets. The work proposed here will lead to measurable improvement in overall accuracy of the 3D macromolecular database on which much of biomedical research depends. This is especially important for "hot" medically-relevant structures because time pressure currently compromises quality in many of these most health-relevant cases.