Distribution of relaxation times on the pico-nano time scales for a functional protein (ABSTRACT)

Folded proteins are functional at relatively elevated temperatures. Below ca. 190-220K, proteins may still display the same average structure, but lack function due to the lack of large size fluctuations that increase nonlinearly with temperature[1]. In this state, proteins are similar to polymers displaying glassy behavior, with their disordered, amorphous character and heterogeneous dynamics. Recently, we provided evidence that the onset of the relevant fluctuations at physiological temperatures occurs with the insertion of an intermediate time scale between the slow -nanosecond time scale- motions due to the activity along the envelope of the energy surface defining the folded protein, and the fast -picosecond time scale- motions of the activity along the pockets decorating the folded-state envelope[2,3]. The intermediate scale was attributed to jumps between the pockets that become possible only when enough energy from the environment is supplied to the system. We now further investigate this time window to analyze the distribution of relaxation times of all relevant motions. The analysis is based on data describing the relaxation phenomena governing the backbone dynamics derived from molecular dynamics simulations of bovine pancreatic trypsin inhibitor, hen egg lysozyme, and cold shock protein, in the temperature region 140-330K. The shifts in the weights of processes contributing to the dynamics and the emergence of new ones at elevated temperatures are displayed. Implications on controllability of function are discussed.