Computational and experimental studies on positive ions derived from peptides

肽衍生正离子的计算和实验研究

• 批准号: 5879-2007
• 负责人: Hopkinson, Alan
• 金额: $ 1.46万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=389220
• 关键词: Computational; experimental; studies; positive; ions

Proteomics relies very heavily on mass spectrometry to determine the sequence of amino acids in at least a short segment of a protein. Usually the protein is broken down by an enzyme (trypsin) and the sequences of the amino acid residues in some of the product peptides are determined by their fragmentation in a mass spectrometry. The mechanisms by which peptides fragment are still not very well understood. We are addressing this problem in several ways. We are examining details of the mechanisms by which protonated peptides (the usual target) fragment; this frequently necessitates looking at the even simpler building blocks of peptides, the amino acids. We are also expanding fragmentation studies into two different classes of ions, (1) radical cations of peptides formed in electrospray mass spectrometry by breaking copper ion / peptide complexes, and (2) complexes of peptides attached to more highly charged ions like a La3+ ion. These two classes of ions will give different types of information about the peptides and will help clear up ambiguities in the sequencing information obtained from the protnated peptide studies. Throughout all this experimental work Density Functional Theory calculations will be used to determine the structures of intermediates and to determine the barriers to their interconversion.

蛋白质组学在很大程度上依赖于质谱法来确定至少一个蛋白质短片段的氨基酸序列。通常蛋白质被一种酶（胰蛋白酶）分解，一些产物多肽中的氨基酸残基序列是通过质谱法测定它们的片段来确定的。多肽断裂的机制还没有被很好地理解。我们正以几种方式解决这个问题。我们正在研究质子化肽（通常的靶标）片段的机制细节；这通常需要研究肽的更简单的组成部分——氨基酸。我们还将碎片化研究扩展到两种不同类型的离子，(1)在电喷雾质谱中通过破坏铜离子/肽复合物形成的肽的自由基阳离子，以及(2)肽与高电荷离子（如La3+离子）连接的复合物。这两类离子将提供关于肽的不同类型的信息，并将有助于澄清从蛋白质化肽研究中获得的测序信息中的歧义。在所有这些实验工作中，密度泛函理论计算将用于确定中间体的结构和确定它们相互转化的障碍。