Assistant Professor

B.S. University of Oregon 1983
Ph.D. University of Washington 1989

Phone:(801) 581-3828

pfflynn@chem.utah.edu

Research Interests 
Our research interests are in the areas of structural biology and biophysics. We are interested in characterizing the function of biologically active macromolecules using a technology-inclusive approach that combines structural studies - primarily using solution NMR - with studies of the biophysical properties of the molecules to elucidate the origins of biological activity. Group projects involve studies of the structure of RNA and DNA oligomers, proteins and their complexes; protein and nucleic acid dynamics; and the energetics and kinetics of biomolecular interactions.

RNA-Protein Interactions
Interactions between polypeptides and RNA oligomers modulate fundamental biological processes. One system studied in our group involves the binding of a large bacterial protein named TRAP (trp-RNA-binding attenuator protein) and the RNA leader sequence present in the tryptophan operon (trp-operon).

In the presence of excess tryptophan TRAP binds a portion (RAT) of the trp-operon with high affinity, whereas at low levels of tryptophan the interaction is much weaker - this distinction leads to highly effective expression-level control of tryptophan biosythesis. Another example involves studies of proteins and RNA oligomers that make up the spliceosome (NHPX - U4SL RNA).

The catalytic activity of the spliceosome is known to arise from a complex orchestration of interactions that occur according to a specific time-order, and we are studying several protein-RNA complexes to elucidate structure and function in this vital eukaryotic process.

Our goal is to provide a structural and dynamical basis for understanding the mechanism by which proteins interact with RNA targets. Approaches include efforts to determine structure using solution NMR methods and to characterize the thermodynamics and kinetics of the interactions based on fluorescence, calorimetry and biosensor techniques.

Macromolecular Dynamics
The importance of internal dynamics in proteins has become increasingly apparent. Solution NMR studies of backbone dynamics indicate that the main-chain atoms are generally highly and homogeneously ordered whereas studies of side-chain motion suggest a more heterogeneous picture. We are interested in probing dynamics across time scales from subnanosecond, through the millisecond regime to seconds and well-beyond. Experiments include longitudinal and transverse relaxation, relaxation dispersion and hydrogen-exchange. Our interests emphasize the characterization of dynamical changes that accompany biomolecular interactions.

Encapsulation of Macromolecules
Proteins, nucleic acid oligomers and other biologically important macromolecules that are normally found in aqueous solution may be encapsulated within a surfactant shell (i.e., dioctyl sulfosuccinate) and transported into non-native solvent systems (i.e., n-alkanes, C3H5 - C5H12). This novel approach opens up new opportunities for solution NMR studies of larger macromolecules as well as fundamental studies of chemical physics using concise, precisely defined environments.

Selected Publications

• Simorellis, A.K., Van Horn, W.D. and Flynn, P. F. Dynamics of Low Temperature Induced Water Shedding from AOT Reverse Micelles. J. Am. Chem Soc. Published ASAP online 3/23/2006
• Ramanchandran, S., Flynn, P. F., Tseng, Y. and Yu, Y. B. Electrostatically Controlled Hydrogelation of Oligopeptides and Proteins. Chem Mater. 17, 6583-6588 (2005)
• Van Horn, W.D., Simorellis, A. K. and Flynn, P. F. Low Temperature Studies of Encapsulated Proteins. J. Am Chem. Soc. 127, 13553-13560 (2005)
• Simorellis, A.K. and Flynn, P.F. A Pulsed Field Gradient NMR Experiment for Translational Diffusion Measurements in Low Viscosity Hydrocarbon Solvents. J. Magn. Reson. 170, 322-325 ( 2004)
• Flynn, P.F. Multidimensional Multinuclear NMR Studies of Encapsulated Macromolecules. Prog. NMR Spectrosc. 45, 31-51( 2004 )
• Flynn, P.F., Wendt, A. and Gollnick, P.G. The influence of Induced Fit in the Interaction of B. Subtilis Tryptophan RNA-Binding Attenuator Protein and its RNA Antiterminator Target Oligomer. Proteins 49, 432-438 (2002).
• Flynn, P.F., Bieber Urbauer, R., Zhang, H., Lee, A.L. and Wand, A.J. Main Chain and Side Chain Dynamics of a Heme Protein: ¹⁵N and ²H NMR Relaxation Studies of R. capsulatus Ferrocytochrome c₂. Biochemistry 40, 6559-6569 (2001).
• Babu, C., Flynn, P.F. and Wand, A.J. Validation of Protein Structure from Preparations of Encapsulated Proteins Dissolved in Low Viscosity Fluids. J. Am. Chem. Soc. 123, 2691-2692 (2001).
• Flynn, P.F., Mattiello, D.B., Hill, H.D.W., and Wand, A.J. Optimal Use of Cryogenic Probe Technology in NMR Studies of Proteins. J. Am. Chem. Soc. 122, 4823-4824 (2000).