New Algorithms and Software for Mass Spectrometric Analysis of Intact Proteins and Complexes

用于完整蛋白质和复合物质谱分析的新算法和软件

基本信息

批准号：
10333416
负责人：
MARSHALL Wayne BERN
金额：
$ 79.58万
依托单位：
PROTEIN METRICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10333416
关键词：
Algorithmic Software Algorithms Antibodies Antibody-drug conjugates Area Automation Binding Biological Biological Assay Biology Bioreactors Bispecific Antibodies Businesses Charge Complex Computer software Computers Country Data Data Analyses Detection Development Devices Dissociation Drug Kinetics Excision Funding Generations Goals Health Human Isotopes Laboratories Ligands Liquid substance Location Mass Spectrum Analysis Methods Monitor Multiprotein Complexes Names Noise Nucleic Acids Ohio Oligonucleotides Pharmaceutical Preparations Phase Protein Analysis Protein Engineering Proteins RNA-Binding Proteins Reporting Resources Sampling Shapes Signal Transduction Speed Surface Testing Texas United States National Institutes of Health Vendor Work algorithm development differential expression dimer drug development experimental study high throughput analysis high-throughput drug screening improved instrument interest ion mobility method development monomer novel nucleic acid binding protein protein complex screening small molecule software development structural biology therapeutic protein vaccine development

项目摘要

Intact proteins and multi-protein complexes represent two of the most important levels of organization in biology, yet these levels are also some of the most difficult to study. Native mass spectrometry provides a means to observe proteins in complex with ligands, other proteins, and nucleic acids. The proposed project will build new algorithms and software for intact and native mass spectrometry. Specifically, the project will further develop Protein Metrics Intact Mass charge-deconvolution software, incorporating multiple information channels (isotope spacing, co-elution, and charge states) into the core algorithm, so that the algorithm can handle complex, low signal-to-noise mass spectra over a wide range of masses and abundances. The project will also build automation software for analyzing data as it is produced by mass spectrometry instruments, naming and organizing files, and producing reports showing results at several levels of detail. The project will enable a number of interesting applications, including small-molecule screening, large-molecule drug comparability, pharmacokinetics, and protein / protein and protein / nucleic acid binding.

完整蛋白质和多蛋白质复合物代表了两个最重要的水平生物学中的组织，但这些层次也是最难研究的层次之一。本国的质谱法提供了一种观察蛋白质与配体复合物的方法，其他蛋白质和核酸。拟议的项目将构建新的算法和软件完整且天然的质谱分析。具体来说，该项目将进一步开发蛋白质完整的质量电荷解卷积软件，包含多个信息通道（同位素间距、共洗脱和电荷态）纳入核心算法，使得算法可以处理各种质量范围内的复杂、低信噪比质谱丰富。该项目还将构建自动化软件，用于分析生成的数据通过质谱仪器，命名和组织文件，并生成报告显示多个细节层次的结果。该项目将实现许多有趣的应用程序，包括小分子筛选、大分子药物可比性、药代动力学和蛋白质/蛋白质和蛋白质/核酸结合。