Integrated Platform for Mass-Spectrometric Studies of Protein Structure

蛋白质结构质谱研究集成平台

• 批准号: 10092176
• 负责人: MARSHALL Wayne BERN
• 金额: $ 61.42万
• 依托单位: PROTEIN METRICS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092176
• 关键词: Address; Amides; Amino Acids; Attention; Binding; Biological Products; Charge; Chemicals; Chromatography; Computer software; Cues; Data; Data Analyses; Deuterium; Dissociation; Dose; Electron Transport; Epitope Mapping; Epitopes; Error Sources; Higher Order Chromatin Structure; Human; Hydrogen; Hydroxyl Radical; Immune response; Individual; Industry; Ions; Label; Laboratories; Ligands; Mass Spectrum Analysis; Measures; Methods; Molecular Conformation; National Institute of General Medical Sciences; Outcome; Pepsin A; Peptide Fragments; Peptide Mapping; Peptides; Phase; Physiologic pulse; Price; Protein Dynamics; Protein Region; Proteins; Proteomics; Reporting; Research; Resolution; Safety; Sales; Side; Signal Transduction; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Software Tools; Solvents; Structure; Sum; Technology; Time; Treatment Efficacy; Universities; Vendor; Vertebral column; Visual; Visualization; Washington; advanced analytics; base; experimental study; functional group; improved; instrument; oxidation; protein structure; search engine; structural biology; three-dimensional visualization; uptake

Summary Technology for studying the higher order structure (HOS) and interactions of biomolecules is a highlighted NIGMS SBIR/STTR research topic. Mass-spectrometric methods for studying HOS include hydroxyl radical footprinting as well as chemical methods to covalently label amino acid side-chain functional groups, and also hydrogen/deuterium exchange (HDX) on protein backbone amides. These methods require only small amounts of not-necessarily-pure material, and can study conformation and dynamics of proteins in solution with or without ligands. Mass spectrometric methods are especially well suited to biopharma comparability and epitope mapping studies. Currently, there is no software that can analyze mass spectrometric data from both covalent labeling and HDX experiments, even though the two methods both probe solvent accessibility and, if combined, would give finer resolution and greater confidence. The outcome will be vendor-neutral commercial software with advanced analytical and reporting capabilities that can handle both HDX and covalent labeling experiments.

概括 研究高阶结构（HOS）和生物分子相互作用的技术是 突出显示了Nigms SBIR/STTR研究主题。研究的质谱法 HOS包括羟基自由基足迹以及共价标记的化学方法 氨基酸侧链官能团，以及氢/氘交换（HDX） 蛋白质骨干酰胺。这些方法仅需要少量的不必要的 材料，可以研究溶液中蛋白质的构象和动力学 配体。质谱法特别适合生物制药可比性 和表位图研究。目前，没有软件可以分析质量 即使这两个实验都来自共价标记和HDX实验的光谱数据 方法既探测溶剂可访问性，否则，如果合并，将提供更好的分辨率和 更大的信心。结果将是供应商中立的商业软件 可以处理HDX和共价标签的分析和报告功能 实验。