Metal binding sites in macromolecular structures

大分子结构中的金属结合位点

基本信息

批准号：
9008644
负责人：
WLADEK MINOR
金额：
$ 34.31万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9008644
关键词：
Algorithms Architecture Area Binding Binding Sites Biochemical Reaction Biological Biological Process Biomedical Research Biophysical Process Cataloging Catalogs Catalysis Chemicals Classification Collection Communities Complement Custom DNA Data Data Set Databases Deposition Detection Development Diagnostic Electron Transport Elements Environment Future Gases Guidelines Heavy Metals Internet Investigation Ions Iron Knowledge Life Machine Learning Magnesium Manuals Maps Metal Binding Site Metal Ion Binding Metals Methodology Mining Modeling Molecular Structure Names Nucleic Acids Nucleotides Online Systems Play Polyphosphates Procedures Production Property Proteins RNA Research Research Personnel Resources Retrieval Role Site Structural Biologist Structure Surveys System Therapeutic To specify Training Update Validation Variant Work Zinc abstracting base comparative computerized tools database structure density design drug discovery electron density experience infancy interest macromolecule model building protein folding protein structure prediction support tools tool

项目摘要

Project: Metal binding environments in macromolecular structures Abstract: Metal ions play vital roles in both the mechanism and architecture of biological macromolecules, including the catalysis of biochemical reactions, electron transport, binding of gases, and stabilization of nucleotides and other polyphosphate compounds. However, a recent survey of publicly available structures of metal-containing proteins and nucleic acids deposited in the PDB revealed an abundance of misidentified and/or sub-optimally modeled metal binding sites. This prompted the creation of a diagnostic tool for the models of metal binding microenvironments, the "CheckMyMetal" (CMM) web server (http://csgid.org/csgid/metal_sites/), which detects geometric and other irregularities in structures of metal binding sites and alerts researchers to potential errors in metal assignment. As the production version of CMM has gained widespread usage, the research community has identified several directions for future development of major interest:1) investigate and validate uncommon heavy metal binding sites in macromolecular structures; 2) establish a server to provide customized subsets of high-quality, validated metal binding sites; 3) develop tools to automatically detect likely metal binding sites in electron density, and identify and add the most probable metal ion during crystallographic model building and refinement; and 4) systematically catalog metal binding architectures and detect new metal binding motifs. The toolkit we propose to develop, using CMM as a basis, contains several modules that will work either independently or as integrated steps in the structure modeling, validation, interpretation and annotation pipeline. This proposal was designed not only for structural biologists to model and validate new structures during crystallographic model building and refinement, but also for a broader audience—biomedical researchers studying metal-containing proteins and nucleic acids.

项目：大分子结构中的金属结合环境摘要：金属离子在生物大分子的机理和结构中起着至关重要的作用，包括生化反应的催化，电子传输，气体结合和稳定核苷酸和其他多磷酸化合物。但是，最近对公开可用结构的调查沉积在PDB中的含金属的蛋白质和核酸显示出了错误识别的抽象和/或次优建模的金属结合位点。这促使创建了一个诊断工具金属绑定微环境的模型，“ checkmymetal”（CMM）Web服务器（http://csgid.org/csgid/metal_sites/），它检测金属结构中的几何和其他不规则性绑定站点和提醒研究人员对金属分配的潜在错误。作为CMM的生产版本研究界已经获得了广泛使用的范围，已经确定了未来发展的几个方向主要感兴趣的：1）研究和验证大分子中不常见的重金属结合位点结构； 2）建立服务器，以提供高质量，经过验证的金属绑定站点的自定义子集； 3）开发工具以自动检测电子密度中可能的金属结合位点，并识别和添加在晶体学模型建立和改进过程中，大多数有问题的金属离子； 4）系统编目金属结构结构并检测新的金属结合基序。我们建议开发的工具包 CMM作为基础，包含几个模块，这些模块将独立或作为集成步骤在结构建模，验证，解释和注释管道。该建议不仅是为结构性生物学家在晶体学模型建设期间建模和验证新结构改进，但也适用于广泛的受众 - 研究含金属蛋白质和的生物医学研究人员核酸。