Research Summary

In my research I use THz (TeraHertz) spectroscopy to directly explore the global and local intermolecular associations in proteins that take place on the picosecond time-scale. I combine experimental measurements with computational analyses to detect and characterize the collective vibrational modes that have been hypothesized to play a central role in determining biochemical activity in proteins and enzymes.

Intrinsic fluctuations in proteins and their role in biological function
The ≤ 100 cm-1 region of the infrared spectrum (the THz regime) is sensitive to global, internal fluctuations that describe the intrinsic dynamics of proteins. These globally, correlated thermal fluctuations allow the protein to sample the ensemble of conformations that make-up the free energy landscape of all possible protein conformations. Therefore, detection and characterization of these fast, structural fluctuations in proteins provides insight into the underlying molecular mechanisms that ultimately determine the outcome of a range biological phenomena such as the selection and propensity for ligand binding or the dynamical associations involved with overcoming energy barriers that trigger the onset of the transition (Tg) toward anharmonic functional motions.

Identifying evolutionary conserved allosteric pathways in protein families
Closely related proteins in a protein family provide a model system for exploring the formation of allosteric perturbation signal pathways that take shape in response to specific protein binding interactions and consequently directly relate to protein functionality. Therefore, protein functional dynamics can be considered as an evolving, landscape created by the interplay between the global, collective fluctuations encoded in the protein structure and the localized protein interactions that define specificity. In my research I use an integrated approach that considers both theoretical methodology involving protein evolutionary patterns and experimental (THz spectroscopy) measurements that directly probe protein intermolecular interactions to identify conserved allosteric signal propagation pathways in protein and enzyme families.

The role of allostery in disease and the use of allosteric modulators in the design of potential drug therapies
I have recently begun to use the knowledge gained from this joint computational-experimental approach on protein networks as a kernel for building the infrastructure for addressing "bigger" questions such as the role of protein allosteric communication in the development of mutational-induced diseases and for addressing the feasibility of more advanced topics such as the rational design of new drug therapies that function as allosteric modulators in a variety of human disorders.


Based on Woods, & Pfeffer (2015). Molecular Biology and Evolution 33, 40-61.

Selected Recent Publications

Woods, K.N., Pfeffer, J., Klein-Seetharaman, J. (2017). Chlorophyll-Derivative Modulation of Rhodopsin Signaling Properties through Evolutionarily Conserved Interaction Pathways. Frontiers in Molecular Biosciences 4, 85. doi:10.3389/fmolb.2017.00085. »Article

Woods, K.N., Pfeffer, J., Dutta, A., Klein-Seetharaman, J. (2016). Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors. Scientific Reports 6:37290. doi:10.1038/srep37290. »Article

Woods, K.N., Pfeffer, J. (2015). Using THz spectroscopy, evolutionary network analysis methods, and MD simulation to map the evolution of allosteric communication pathways in c-type lysozymes. Molecular Biology and Evolution 33, 40-61. doi:10.1093/molbev/msv178. »Article

Woods, K.N. (2014). Using THz time-scale infrared spectroscopy to examine the role of collective, thermal fluctuations in the formation of myoglobin allosteric communication pathways and ligand specificity. Soft Matter 10 (24), 4387-4402. doi: 10.1039/C3SM53229A. »Article

Woods, K.N. (2014) The glassy state of crambin and the THz time scale protein-solvent fluctuations possibly related to protein function. BMC Biophysics 7:8. doi:10.1186/s13628-014-0008-0. »Article