Influence of Peptide Structure on Dissociation

蛋白质在生物体中起着核心作用，例如，作为酶 作为结构或机械单位，以及作为细胞信号传导， 分子。蛋白质组学领域，需要大规模的鉴定和结构分析， 蛋白质的表征，强烈依赖于串联质谱（MS/MS） 和利用MS/MS谱的数据库搜索。这个项目的首要目标是 一个建议是通过串联质谱改进自动化肽和蛋白质鉴定 光谱法拟议的研究将确定和全面表征 由两个主要的互补序列激活的肽的片段化行为 MS/MS活化方法、电子转移解离（ETD）和碰撞-质谱（MS/MS）活化方法。 激活解离（CAD），当两者都应用于两个突出的仪器时， 用于蛋白质组学实验的平台（线性离子阱和四极飞行时间， QTOF）。指导这项研究的基本假设是，计算机算法 用于肽和蛋白质测序、鉴定和定量， 嵌入式数据采集软件，可以通过统计分析如何改进 肽在分子水平上的片段。不同的行为的先验知识 氨基酸为观察到的可能的片段化模式提供了重要的见解 和MS/MS光谱，这些数据将用于改善数据采集和数据 分析.这项研究汇集了三个研究小组，威索基小组和 在肽片段化机制和数据挖掘方面的专业知识，Tseng小组与 生物统计学/生物信息学方面的专业知识（执行聚类加分类， 大型光谱数据集的回归树分析），以及Coon集团， 在线性离子阱/轨道阱质谱仪中的电子转移解离（ETD）。

Proteins play a central role in living organisms, serving, for example, as enzymes that catalyze metabolic reactions, as structural or mechanical units, and as cell signaling molecules. The field of proteomics, which entails large scale identification and structural characterization of proteins, depends strongly on tandem mass spectrometry (MS/MS) and database searches that make use of MS/MS spectra. The overarching goal of this proposal is to improve automated peptide and protein identification by tandem mass spectrometry. The proposed research will identify and comprehensively characterize clusters of fragmentation behavior for peptides activated by two major complementary MS/MS activation methods, electron transfer dissociation (ETD) and collisionally- activated dissociation (CAD), when both are applied in two prominent instrument platforms used for proteomics experiments (linear ion trap and quadrupole time-of-flight, QTOF). The underlying hypothesis guiding this research is that the computer algorithms that are used for peptide and protein sequencing, identification, and quantitation, and the embedded data acquisition software, can be improved by statistically analyzing how peptides fragment at a molecular level. A priori knowledge of the behavior of differenct amino acids provides significant insight into the possible fragmentation patterns observed and the MS/MS spectra and these data will be used to improve data acquisition and data analysis. This research brings together three research groups, the Wysocki group with expertise in peptide fragmentation mechanisms and data mining, the Tseng group with expertise in biostatistics/ bioinformatics( to perform clustering plus classification and regression tree analysis of large spectral datasets), and the Coon group, developers of electron transfer dissociation (ETD) in the linear ion trap/Orbitrap mass spectrometer.