MolProbity Service and Related 3D-Analysis Resources

MolProbity 服务和相关 3D 分析资源

• 批准号: 7069249
• 负责人: DAVID Claude RICHARDSON
• 金额: $ 26.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7069249
• 关键词: Internet; bioengineering /biomedical engineering; bioinformatics; chemical structure; computational biology; computer data analysis; computer graphics /printing; computer program /software; computer system design /evaluation; functional /structural genomics; macromolecule; nuclear magnetic resonance spectroscopy; nucleic acid structure; proteomics; structural biology

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.

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功能、用户友好性、通用性、健壮性、可维护性和可扩展性，以使许多当前用户（今年有11500个工作会议）以及现在希望使用它的更广泛的生物医学研究人员社区受益。MOLPROBITY有两个独特的功能可以实现这些目标。1是带有显式氢的全原子接触分析，它以前所未有的细节显示了空间接触，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MAGE和KING中实现的运动学图形概念，强调交互性和对3D关系的清晰感知。自1992年以来，这个开源、跨平台的软件家族支持结构生物学、生物化学、生物信息学、教育甚至非分子应用。新的蛋白质数据库网站和数据沉积利用了这些验证和图形工具。大多数结构基因组学中心都采用了MOLPROBITY，但希望进一步调整其生产管道的需求。这个项目将使开发和文档在纯粹的研究工作中难以证明，但对于作为开放资源的长期生存和增长至关重要。支持将增加结构比较，mmCIF文件，并分析核磁共振集合和核酸。程序将被重新组织以实现模块化，并为重用提供更好的文档。MOLPROBITY的web界面将进行修改，既可以直观地简化沉积结构的评估，也可以为结构生物学专家客户解决新问题提供强大的灵活性。预先计算的数据库和来自其他网站的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服务接口将为新的预测和生物信息学用户提供分析数千个文件的服务。用户/合作者的反馈，来自我们计算机科学合作者的建议，以及我们自己在研究中使用系统的经验将指导这个软件开发过程。在公共卫生方面，MOLPROBITY可以帮助新药物的计算设计取得成功，特别是在时间有限的情况下（例如针对SARS），因为它可以帮助用户快速评估和提高实验确定的药物靶点模型的准确性。这里提出的工作将导致三维大分子数据库的总体精度的显著提高，而生物医学研究依赖于三维大分子数据库。这对于“热门”医学相关的结构尤其重要，因为时间压力目前影响了许多这些与健康最相关的病例的质量。