CAREER: Thioamides as Minimalist Chromophores to Monitor Protein Dynamics

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

The Chemistry of Life Sciences Program funds Professor E. James Petersson of the University of Pennsylvania for a CAREER award to carry out research entitled "Thioamides as Minimalist Chromophores to Monitor Protein Dynamics." This project involves the study the molecular details of protein motions. The goal of the research program is to develop novel, "non-invasive" probes that will be used to monitor changes in protein structure with increased levels of structural resolution. A long-term goal is to create experimentally-constrained molecular dynamics trajectories (essentially atomic-scale movies) of protein motions. The probes themselves consist of single-atom O-to-S substitutions to the amide bond that links every amino acid in a protein. The probes have a very small size, so that unlike many current probes, they will not perturb the motion they are meant to study. Once fully developed, this probe has the potential to provide detailed, time-resolved information on the motions of individual amino acids in the protein. Understanding concerted changes resulting from large numbers of non-covalent interactions is a problem not only for Biochemistry, but for nearly all scientific study at the nanometer scale. In the course of developing thioamides for motional studies, a greater understanding of this relatively unexplored functional group will be obtained, with regard to both electronic and physical properties. Structural rearrangements in proteins are often important to cell signaling and protein misfolding in disease. Thioamide probes can be of utility to any member of the biological community wishing to study protein motion and may improve community's ability to design molecular motors from first principles. The broader impacts of this work include training undergraduate and graduate students in a multidisciplinary laboratory environment that makes use of organic synthesis, physical chemistry, molecular, and cellular biology to investigate biological phenomena. Other activities supported by this grant include the creation of a Future Faculty program to help to train students and postdoctoral scholars with academic aspirations. The is actively engaged in educational outreach activities targeted toward middle school students, an age group where scientific interest is often gained and lost. Mentoring students as budding research scientists occurs by engaging students in the design of experiments and publication of results. Mentoring them as budding teachers occurs through their involvement in intramural and extramural educational activities. This project is receiving co-funding from the Biomolecular Dynamics, Structure and Function Cluster in the Division of Molecular and Cellular Biosciences.