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、动力学和机理(CSDM-A)以及化学测量和成像(CMI)项目支持锡耶纳学院的George L.Barnes教授研究多肽分子如何在气相中发生高能碰撞后解体或粘连到表面。当使用被称为质谱仪的仪器对分子进行分析时，这种碰撞就会发生。质谱仪根据分子的质量和电荷识别分子及其碎片。质谱分析的准确性取决于对碰撞的理解程度。这个项目考察了分子形状和常见生物修饰对碰撞和碰撞产生的分子产物的重要性。蛋白质是由称为核糖体的分子机器在活细胞中合成的，核糖体将信使核糖核酸(MRNA)中存储的信息转化为蛋白质。蛋白质翻译后的修饰被称为“翻译后”修饰(PTM)。巴恩斯教授对PTM如何影响气相碰撞的结果特别感兴趣。该项目积极邀请本科生研究人员参加，他们在理论和实验方法方面都接受了交叉培训，并有机会在全国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学(MS2)相关的模型系统。特别是，选择了一系列质子化肽及其翻译后修饰的版本来研究二级结构对软着陆和碰撞诱导解离的影响。这项研究阐明了非共价相互作用和多肽片段的复杂形成的重要性。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学。除了获得关于分子碰撞和反应的基本见解外，该项目还对优化生物分子的质谱学实验和解释结果数据具有直接影响。反过来，这项研究可能会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教授的合作为Barnes教授的锡耶纳学院的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NSF的法定使命，并通过使用基金会的智力优势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.