ISOTOPE SIGNATURE BASED IDENTIFICATION OF CROSSLINKED PEPTIDES BY MS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蛋白质结构和蛋白质间相互作用的知识对于我们理解生物过程是必不可少的。获取此类知识往往是一项严峻的挑战。蛋白质交联和质谱学(MS)的最新进展已经显示出对这一领域做出贡献的巨大潜力。在这里，我们正在开发一种新的方法，基于其在H218O存在下消化时的独特同位素特征，快速而准确地识别交联肽。这种方法克服了其他技术所需的特殊合成交联剂和/或多次MS运行的需要。我们将通过分析已知结构的蛋白质/复合体来验证我们的方法。计算技术Rosetta将被修改，以验证根据已公布的原子结构观察到的交联键。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Knowledge of protein structures and protein-protein interactions is essential for our understanding of biological processes. Obtaining such knowledge often presents a severe challenge. Recent advances in protein crosslinking and mass spectrometry (MS) have shown significant potential to contribute to this area. Here we are developing a novel method to rapidly and accurately identify crosslinked peptides based on their unique isotope signature when digested in the presence of H218O. This method overcomes the need for specially synthesized crosslinkers and/or multiple MS runs required by other techniques. We will validate our method by analyzing proteins/complexes of known structure. The computational technique Rosetta will be modified to validate crosslinks observed against published atomic structures.