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

Siena University, Loudonville NY

Investigators

Abstract

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.