Structural Biology Information Resources

结构生物学信息资源

• 批准号: 8149595
• 负责人: stephen h bryant
• 金额: $ 665.96万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149595
• 关键词: Address; Binding; Information Resources; Protein Family; protein structure; structural biology

Protein three-dimensional structures are drawn from the Protein Data Bank (PDB), an international database collaboration supported in part by the NIH. PDB records are processed at NCBI to provide Molecular Modeling Database (MMDB) records with precise definitions of the component biological macromolecules and chemicals, and their interactions as indicated by atomic contacts in three-dimensional structure. Protein structure records are compared to NCBI protein sequence records using the Basic Local Alignment Search Tool algorithm (BLAST) and compared to one another by the Vector Alignment Search Tool structure-comparison algorithm (VAST). Protein sequences in the NCBI collection are also compared to protein family records in the Conserved Domain Database (CDD) using the Reverse Position-Specific BLAST algorithm (RPSB). These automated comparison methods provide the cross references needed to link protein and gene sequences in NCBI's extensive collection to the biological function annotation provided by protein structures. Informatics projects were needed this year to address ongoing "remediation" undertaken by PDB, who have more than once modified 100% of the over 65,000 files in their collection. "Remediation" of the bonded-atom connectivity (chemical graphs) of component molecules has fortunately become less frequent. And additional, potentially useful information is now provided, such as "SPLIT" records indicating when a given crystal structure has been divided into two or more PDB files, and "Biological Assembly" information indicating a subset of biologically important interactions. Unfortunately the additional information is encoded in "REMARK" text without documented formats, requiring considerable effort to develop reliable text-parsing algorithms. But correction of PDB "SPLIT" files and display of "Biological Assembly" information on MMDB "Document Summary" and "Structure Summary" pages has progressed, and public release is expected before the end of this year. Research to identify molecular interactions not included in the PDB "Biological Assembly" has continued. This includes identification of contact thresholds for biologically relevant protein-ligand complexes such as heme in hemoglobin, and interactions observed among related protein structures but not mentioned the PDB files of those structures. The Inferred Biomolecular Interactions Server (IBIS) http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.cgi has been greatly improved, providing a research tool for structural biologists to explore the variety of intermolecular interactions observed among related protein three-dimensional structures. The NCBI Conserved Domains database CDD is in part derived from comprehensive protein sequence alignment collections prepared automatically by others. These include, for example, the Pfam collection prepared at the Wellcome Trust Sanger Institute and the Protein Clusters collection prepared at NCBI/IEB. More important contributions to CDD are the expert-curated protein family alignments prepared by staff of the CDD project. Very accurate protein family alignments consistent with known three-dimensional structures and structural superpositions are prepared using algorithms within the "See in Three Dimensions" program (Cn3D). Conserved subfamilies consistent with evolutionary evidence are derived using phylogenetic tree algorithms and graphics within the "Conserved Domain Tree" program (CDTree). Curators save into CDD records the phylogenetic trees identifying ancient conserved subfamilies and the biological function annotation derived from interactions observed in three-dimensional structures within each subfamily and/or from other observations such as subfamily-specific experimental studies reported in the literature. CDD informatics projects have continued this year. An algorithm to automate refinement of CDD subfamily alignments by rapidly performing multiple realignments of member sequences has continued to prove useful in reducing curator effort. A batch CD-search service supporting easy retrieval of CDD alignments and functional annotations for large groups of sequences has now been released and is in wide use. A research project on automated identification of ancient conserved multi-domain architectures has also continued and appears successful. The goal is to support efficient construction of ancient conserved multi-domain CDD records based on previously-curated alignments of component domains. This will allow curators to provide multi-domain-specific functional annotation without the necessity to edit already-accurate alignments. Another research project continued this year aims to automate identification of ancient conserved subfamilies where accurate biological function annotation is likely, given known three-dimensional structures and/or literature citations for subfamily member sequences. If successful, this procedure will reduce the curator time required to browse often-large phylogenetic trees produced by CDTree, supporting efficient identification of subfamilies where functional annotation is most possible and worthwhile.

蛋白质三维结构取自蛋白质数据库 (PDB)，这是一个由 NIH 部分支持的国际数据库合作组织。 PDB 记录在 NCBI 进行处理，以提供分子建模数据库 (MMDB) 记录，其中包含生物大分子和化学物质成分的精确定义，以及通过三维结构中的原子接触指示的它们的相互作用。使用基本局部比对搜索工具算法 (BLAST) 将蛋白质结构记录与 NCBI 蛋白质序列记录进行比较，并通过矢量比对搜索工具结构比较算法 (VAST) 进行相互比较。还使用反向位置特异性 BLAST 算法 (RPSB) 将 NCBI 集合中的蛋白质序列与保守域数据库 (CDD) 中的蛋白质家族记录进行比较。这些自动比较方法提供了将 NCBI 广泛收集的蛋白质和基因序列与蛋白质结构提供的生物功能注释联系起来所需的交叉引用。 今年需要信息学项目来解决 PDB 正在进行的“修复”问题，PDB 不止一次修改了其收藏的 65,000 多个文件中的 100%。幸运的是，对组成分子的键合原子连接性（化学图​​）的“修复”已经变得不那么频繁了。现在还提供了其他潜在有用的信息，例如指示给定晶体结构何时被划分为两个或多个 PDB 文件的“SPLIT”记录，以及指示生物学上重要的相互作用的子集的“生物组装”信息。不幸的是，附加信息以“备注”文本进行编码，没有记录格式，需要付出相当大的努力来开发可靠的文本解析算法。但PDB“SPLIT”文件的修正以及MMDB“文档摘要”和“结构摘要”页面上“生物组装”信息的显示已经取得进展，预计在今年年底前公开发布。鉴定 PDB“生物组装”中未包含的分子相互作用的研究仍在继续。这包括识别生物学相关的蛋白质-配体复合物（例如血红蛋白中的血红素）的接触阈值，以及观察到的相关蛋白质结构之间的相互作用，但没有提到这些结构的 PDB 文件。推断生物分子相互作用服务器 (IBIS) http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.cgi 已得到极大改进，为结构生物学家提供了一个研究工具，用于探索观察到的各种分子间相互作用相关蛋白质三维结构。 NCBI 保守域数据库 CDD 部分源自其他人自动准备的全面蛋白质序列比对集合。例如，这些包括在 Wellcome Trust Sanger Institute 准备的 Pfam 集合和在 NCBI/IEB 准备的 Protein Clusters 集合。对 CDD 更重要的贡献是由 CDD 项目工作人员准备的专家策划的蛋白质家族比对。使用“See in Three Dimensions”程序 (Cn3D) 内的算法制备与已知三维结构和结构叠加一致的非常准确的蛋白质家族比对。与进化证据一致的保守亚科是使用“保守域树”程序（CDTree）中的系统发育树算法和图形得出的。策展人将识别古代保守亚科的系统发育树和从每个亚科内三维结构中观察到的相互作用和/或其他观察结果（例如文献中报告的亚科特定实验研究）得出的生物功能注释保存到 CDD 记录中。 CDD信息学项目今年仍在继续。通过快速执行成员序列的多次重新比对来自动细化 CDD 亚家族比对的算法已继续证明在减少管理者工作方面很有用。批量 CD 搜索服务支持轻松检索大量序列的 CDD 比对和功能注释，现已发布并得到广泛使用。一个关于古代保守多域架构自动识别的研究项目也在继续进行，并且似乎取得了成功。目标是支持基于先前策划的组件域对齐来有效构建古代保守的多域 CDD 记录。这将允许策展人提供多领域特定的功能注释，而无需编辑已经准确的对齐。今年继续进行的另一个研究项目旨在自动识别古代保守亚科，在已知的三维结构和/或亚科成员序列的文献引用的情况下，可能会进行准确的生物学功能注释。如果成功，该过程将减少浏览 CDTree 生成的通常较大的系统发育树所需的管理时间，支持有效识别最有可能且最值得进行功能注释的亚科。