Escaping the Water Cage: Protein Intramolecular Vibrations and the Dynamical Transition

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The protein dynamical transition is the remarkable increase in the average atomic root mean squared displacement (RMSD) in the 180-220 K range. The effect is associated with the onset of anharmonic motions critical to biological function. However evidence of the actual biological relevance of the dynamical transition is inconsistent. While for some proteins, function ceases below the dynamical transition, for other proteins the dynamical transition appears to have no effect. Here we report measurements that suggest the difference arises from the dependence of function on large scale conformational change, and specifically the reliance on long range vibrations to access these structural changes. The dynamical transition has been extensively observed using X-ray, neutron scattering, NMR and terahertz absorption spectroscopy [1,2], with the results indicating it arises from thermally activated solvent motions. Those techniques measure all motions contributing to the RMSD including both localized motions and intramolecular vibrations. To isolate the vibrations and examine how the dynamical transition impacts them, we use a new technique, anisotropy terahertz microscopy (ATM) [3]. This unique method suppresses the background from the localized motions giving unprecedented access to the long range motions that enable large scale conformational changes. ATM measurements of lysozyme anisotropic optical absorbance in the 150-300 K temperature range show that the resonant vibrational bands rapidly increase in intensity at the dynamical transition, and surprisingly blue shift with increasing temperature, in contrast to the expected anharmonicity. The measurements demonstrate that the surrounding solvent below the dynamical transition acts as a frozen cage preventing the vibrations necessary for functional conformational change. This solvent slaving of the long range vibrations potentially impacts protein structural stability and vulnerability to structural disorder. This work was supported by NSF (DBI 1556359 and MCB 1616529), and DOE DE-SC0016317. 1. Doster,W., et al. Phys.Rev.Lett., 2010.104(9):098101. 2. Niessen,K., et al. Biophys.Rev., 2015.7,201. 3. Acbas,G., et al. Nat.Commun., 2014.5,3076.