RUI: Simulations of MS2 spectra: An examination of post-translational modification, secondary structure, and non-covalent complexes

化学系的化学结构、动力学和机制（CSDM-A）和化学测量和成像（CMI）项目支持锡耶纳学院的乔治·l·巴恩斯教授研究肽分子在气相高能碰撞后如何分解或粘在表面上。这种碰撞发生在使用质谱仪分析分子时，质谱仪根据分子的质量和电荷来识别分子及其碎片。质谱分析的准确性取决于对碰撞的理解程度。该项目考察了分子形状和常见的生物修饰对碰撞和碰撞产生的分子产物的重要性。蛋白质是在活细胞中由称为核糖体的分子机器合成的，核糖体将储存在信使核糖核酸（mRNA）中的信息翻译成蛋白质。蛋白质在翻译后的修饰称为“翻译后”修饰（PTMs）。Barnes教授对ptm如何影响气相碰撞的结果特别感兴趣。本项目积极招收本科生研究人员，他们在理论和实验方法上进行交叉训练，并有机会在国家会议和其他科学会议上展示他们的成果。采用计算和实验相结合的方法，重点研究了与串联质谱（MS2）相关的模型系统。特别地，我们选择了一系列质子化肽及其翻译后修饰肽来研究二级结构对软着陆和碰撞诱导解离的影响。该研究阐明了非共价相互作用和肽片段复杂形成的重要性。方法包括直接动力学模拟、从头计算、速率计算和实验串联质谱法。除了获得关于分子碰撞和反应的基本见解外，该项目还对生物分子质谱实验的优化和结果数据的解释具有直接意义。反过来，这项研究可能对更广泛的生物和健康相关科学产生重要影响。与普渡大学的Julia Laskin教授合作，为Barnes教授的锡耶纳学院学生研究人员提供了在大型研究型大学背景下的宝贵经验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemical Structure, Dynamics, and Mechanisms (CSDM-A) and Chemical Measurement and Imaging (CMI) Programs of the Division of Chemistry support Professor George L. Barnes at Siena College to study how peptide molecules fall apart or stick to surfaces following high-energy collisions in the gas phase. Such collisions occur when molecules are being analyzed using instruments called mass spectrometers, which identify molecules and their fragments according to their mass and electric charge. The accuracy of the mass spectral analysis depends on how well the collisions are understood. This project examines the importance of the molecular shape and of common biological modifications on the collisions and the molecular products generated by the collisions. Proteins are synthesized in living cells by molecular machines called ribosomes, which translate the information stored in messenger ribonucleic acid (mRNA) into proteins. Modifications of the proteins after translation are called "post-translational" modifications (PTMs). Prof. Barnes is especially interested in how the PTMs affect the outcomes of gas phase collisions. This project actively involves undergraduate student researchers who are cross-trained in both theoretical and experimental methods and have the opportunity to present their results at national conferences and other scientific meetings. A combined computational and experimental approach is taken that focuses on model systems relevant to tandem mass spectrometry (MS2). In particular, a range of protonated peptides and their post-translationally modified versions are selected to investigate the impact of secondary structure on soft landing and collision-induced dissociation. The study elucidates the importance of non-covalent interactions and complex formation of peptide fragments. Methods include direct dynamics simulations, ab initio calculations, rate calculations, and experimental tandem mass spectrometry. In addition to the fundamental insights gained regarding molecular collisions and reactions, the project has direct implications for the optimization of mass spectrometric experiments on biomolecules and the interpretation of the resulting data. In turn, the research may have important implications for a wider range of biological and health-related sciences. Collaboration with Prof. Julia Laskin at Purdue University is providing valuable experience in the large research university context for Prof. Barnes' Siena College student researchers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.