Conformational Dynamics and the Energy Landscape of Calmodulin

University Of Kansas Center For Research Inc, Lawrence KS

Investigators

Abstract

In this award, funded by the Experimental Physical Chemistry Program of the Chemistry Division and the Molecular Biophysics Program of the Molecular and Cellular Biosciences Division of the Biology Directorate, Prof. Carey Johnson and Prof. John P. Ralston of the University of Kansas and their graduate and undergraduate student colleagues will develop advanced single-molecule fluorescence correlation spectroscopy techniques for studying the long-time (microsecond - millisecond) conformational dynamics of Calmodulin -- a calcium signaling protein. The goals of these studies are to simultaneously study the conformational dynamics of a biologically important protein whilst developing advanced biophysical techniques that can be applied by other researchers to other problems in protein dynamics. Some important dynamical processes in proteins take up to milliseconds to occur. This is a problematical time range for most theoretical and experimental techniques -- there is a missing tool in the scientific toolbox for physical scientists who wish to understand how proteins work in biological systems. Profs. Johnson, Ralston and their student collaborators wish to develop this tool. In the course of doing this, they will try to unravel the inner workings of an important calcium binding protein, Calmodulin, which functions as a molecular switch, as it responds to calcium ion signals and activates target enzymes in a number of biological pathways. The research is interdisciplinary, and will provide the students working on it with unique skills in the physical and biological sciences. In addition, the undergraduates working on this project will be recruited from the University of Kansas and Haskell Indian Nations University Bridge Project. The single-molecule analysis software developed over the course of this project will be broadly disseminated via a website.