Hydration and temperature interdependence of protein picosecond dynamics

Abstract

We investigate the nature of the solvent motions giving rise to the rapid temperature dependence of protein picoseconds motions at 220 K, often referred to as the protein dynamical transition. The interdependence of picoseconds dynamics on hydration and temperature is examined using terahertz time domain spectroscopy to measure the complex permittivity in the 0.2-2.0 THz range for myoglobin. Both the real and imaginary parts of the permittivity over the frequency range measured have a strong temperature dependence at >0.27 h (g water per g protein), however the permittivity change is strongest for frequencies <1 THz. The temperature dependence of the real part of the permittivity is not consistent with the relaxational response of the bound water, and may reflect the low frequency protein structural vibrations slaved to the solvent excitations. The hydration necessary to observe the dynamical transition is found to be frequency dependent, with a critical hydration of 0.19 h for frequencies >1 THz, and 0.27 h for frequencies <1 THz. The data are consistent with the dynamical transition solvent fluctuations requiring only clusters of ~5 water molecules, whereas the enhancement of lowest frequency motions requires a fully spanning water network.

Terahertz dynamics of amorphous (Bio) pharmaceutical mixtures

“…There is no clear onset of local mobility around 0.67 T g in such systems. Instead, the increase in the terahertz absorption is continuous much like the observations made by neutron scattering [8] and previous terahertz spectroscopy studies [9].…”

Direct measurement of molecular mobility and crystallisation of amorphous pharmaceuticals using terahertz spectroscopy

“…In all these discussions it was assumed that water molecules that are in direct contact with the protein must play a key role in the change in flexibility associated with the dynamical transition. More recent studies from the same group using powder samples of myoglobin that were carefully equilibrated to different water content highlighted that this effect alone cannot explain the dynamical transition but that the vibrational response of the protein itself appears to play a significant role [101].…”

Probing temperature- and solvent-dependent protein dynamics using terahertz time-domain spectroscopy

“…The electric field of the THz radiation will interact with motions within the system that cause a change in dipole moment (Decius & Hexter, 1977). In simple molecular crystals this has been shown to take the form of a summation of lowfrequency harmonic normal modes, which can be approximated by Lorentzian dipoles (Burnett et al, 2013;Lipps et al, 2012). In liquids or amorphous systems that show no longrange order, and thus no low-frequency collective vibrational normal modes, rotational motions on these time scales are linked with the dielectric permittivity of the system and are often represented by a summation of Debye relaxations (Schrö der & Steinhauser, 2010;Lipps et al, 2012) or a Havriliak-Negami function (Schrö der & Steinhauser, 2010;Sun et al, 2012;Sibik et al, 2013).…”