NSF Postdoctoral Fellowship in Biology FY 2010

Robustelli Paul J, Cross River NY

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship for FY 2010. The fellowship supports a research and training plan entitled "Experimental and Computational Investigation of the Role of Protein Conformational Dynamics in Enzymatic Activity" for Paul Robustelli. The host institution for this research is Columbia University, and the sponsoring scientist is Author G. Palmer III. The biological functions of proteins are dictated by both their structures and their conformational dynamics. In many cases characterizing the conformational dynamics of a protein has been shown to be essential in understanding how it carries out its biological function and how it interacts with other molecules, and has provided valuable insights into molecular mechanisms of catalysis, recognition, signaling, and the binding of drugs to pharmaceutical targets. In this project, new computational techniques are developed to characterize how differences in conformational dynamics dictate the variable enzymatic activities in a family of structurally similar Ribonuclease enzymes involved in DNA replication, repair, and transcription. These techniques combine the interpretation of experimental measurements, made with nuclear magnetic resonance, with molecular dynamics computer simulations to elucidate, and thermodynamically characterize, the conformational dynamics of proteins at atomic resolution. This investigation determines the role of protein dynamics in mechanisms of enzymatic catalysis for a biologically important class of enzymes and creates new freely distributed computational tools that can be used to understand the link between protein dynamics and function in numerous biological processes. Training goals include learning experimental protein structure and dynamics measurements using nuclear magnetic resonance and developing computational skills in novel protein structure calculation techniques and molecular dynamics simulations. This research is integrated with the mentoring of research students and results are incorporated into special topics lectures in courses on molecular biophysics and nuclear magnetic resonance of macromolecules at Columbia University.