Measuring Protein Intramolecular Dynamics with Terahertz Light: Functional Changes and Relevance to Biology

As Austin and coworkers showed over 45 years ago [1], thermally activated motions are critical to protein function, however the characterization of these motions has been challenging. In the last 20 years new optical instrumentation in the critical terahertz (THz) frequency range has enabled unprecedented characterization of these dynamics revealing changes in the collectivity and orientation of motions with functional state for enzymes and photoactive proteins [2-5]. In this talk I will review measurements of protein intramolecular vibrations, their directionality and their impact on steering function. The various shortcomings of standard simulation methods to analyze the optical results will be discussed as well as possible strategies to overcome these. This work was supported by National Science Foundation MRI^2 grant DBI2959989, IDBR grant DBI1556359, and MCB grant MCB1616529, and the Department of Energy BES grant DE-SC0016317.
1. Austin, R.H., et al., Dynamics of Ligand Binding to Myoglobin. Biochemistry, 1975. 14(24): p. 5355-5373.
2. Falconer, R.J. and A.G. Markelz, Terahertz Spectroscopic Analysis of Peptides and Proteins. J. Infrared, Millimeter and THz Waves, 2012. 33: p. 973-988.
3. Niessen, K.A., et al., Moving in the Right Direction: Protein Vibrational Steering Function. Biophysical Journal, 2017. 112(5): p. 933-942.
4. Niessen, K., M. Xu, and A.G. Markelz, Terahertz optical measurements of correlated motions with possible allosteric function. Biophysical Reviews, 2015. 7: p. 201-216.
5. Acbas, G., et al. Optical measurements of long-range protein vibrations. Nature Communications, 2014. DOI: 10.1038/ncomms4076.