Dynamics and Function of Proteins by NMR and Computation

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Detailed information about protein structure and dynamics at an atomic level is of fundamental importance for understanding protein stability, interactions, and function. The overall goals of this project are the development of new methods for a comprehensive description of complex dynamics of proteins by combining NMR spectroscopy with advanced computer simulations and the application of these methods to biologically important molecular systems. To achieve these objectives, NMR chemical shifts of all amino acid side-chains will be quantitatively parametrized in terms of their structure and environment using databank information and molecular dynamics trajectories into the microsecond range. They will permit the rigorous assessment of the quality of protein ensembles such as ones generated by long molecular dynamics trajectories. These tools together with experimental NMR will be applied for the improvement of the accuracy of low-resolution protein structures and for the characterization of allosteric regulation and high-plasticity ligand binding. The project will produce new algorithms, web servers, and software for the increasingly accurate and realistic characterization of proteins in their native environment. The combination of NMR spectrosccopy with high-performance computation will be applicable to a wide range of biomolecular systems. These tools will be made available to the structural biology, biophysics, and biomolecular NMR communities. This project will provide interdisciplinary training and research opportunities for undergraduate students in FSU's "Honors in the Major program", graduate students, and postdocs at the Department of Chemistry and Biochemistry at Florida State University (FSU), at the Institute of Molecular Biophysics at FSU, and at the National High Magnetic Field Laboratory (NHMFL), with significant numbers of students from demographically underrepresented groups. Research methods and results will be incorporated into undergraduate and graduate courses on biophysics and biomolecular spectroscopy. Selected examples of this research will be presented at the annual Open House at the NHMFL, which attracts a broad cross section of the population of North Florida and its vicinity, helping to increase scientific literacy of the public. An assistant professor at Bethune-Cookman University (BCU), a historically black college in Florida, will be provided space and resources to spend each summer in the PI's lab, which will count toward his professional development activities. He will bring minority undergraduate students with him from BCU to carry out research on NMR parameter calculations and analysis.