Structures of Gas-Phase Protein Ions

Indiana University, Bloomington IN

Investigators

Abstract

This research program entitled "Structures of Gas-Phase Protein Ions" represents a significant expansion of the prior work of Dr. David Clemmer of Indiana University at Bloomington and is supported by the Analytical and Surface Chemistry program. The goal of this research is to investigate the 3-dimensional conformation of gas-phase proteins and peptides using a modified ion mobility/time of flight mass spectrometer. The instrumentation to be used can accommodate a high number of analyses, which will enable the screening of large libraries of compounds. Chemical probes, such as hydrogen-deuterium (H/D) exchange reactions, will be used to investigate both conformation and reactivity. The novel experiments planned, which couple H/D exchange studies with collision induced dissociation experiments, may result in an important new technique for interpreting and measuring H/D exchange data. The correlation between solution phase and gas phase protein conformations is not well defined, and may not be similar to solution phase conformations. However, if a correlation is found, this research could have a major impact on the understanding of the chemical mechanisms of biological reactivity and the study of protein structure/reactivity relationships. With the increased understanding of the role of proteins in biological systems, it is now known that the 3-dimensional structure of a protein directly effects the function to be performed by the protein. Thus, an important area of chemical research today is the development of techniques to establish the 3-dimensional structure. In this fundamental research by Professor Clemmer, he will develop a new technique to examine protein structure. This research, though high risk, has the potential to impact society in the future through improved understanding of disease mechanisms based on protein structure/function relationships. This will lead to enhancements in pharmaceutical development and treatment of disease.