Comprehensive Error Analysis in NMR Relaxation for Accurate Assessment of Protein Dynamics

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

During the past two decades, advances in NMR and its related technologies have tremendously increased the sensitivity of NMR relaxation experiments. NMR-derived parameters now have sufficient sensitivity to allow comparison with parameters obtained by other methods, such as molecular dynamics simulations and thermodynamics experiments. However, for meaningful results to emerge and for reasonable comparison of NMR-derived dynamics with those obtained by other methods, accurate evaluation of uncertainties in the NMR-derived parameters is critical. The objective of this project is to provide a comprehensive assessment of the relaxation errors for a variety of experiments. Based on this assessment, uncertainty estimations will be incorporated into software packages to allow accurate extraction of protein dynamics. Such analyses will significantly impact the field and are crucial at the present time when NMR dynamics studies are increasingly used to interpret unique features in enzymatic mechanisms and other biological processes. The results of this research will be widely distributed via journal publications and websites, promoting their broad application in the NMR community and facilitating the development of new and existing analysis tools in the field. Removing impediments caused by improper error estimation, this work will allow the merging and integration of NMR results with those derived by other biophysical methods. Such seamless integration is important for future progress in Biophysics and Structural Biology. This project will also provide interdisciplinary training for students. An advanced NMR course comprising theory and experiments will be integrated into the Molecular Biophysics and Structural Biology Graduate Curriculum and increased opportunities for summer undergraduate research will be created. Also, science exposure in the local communities will be increased and Structural Biology will be brought to K-12 schools.