Glassiness and coupling of time scales in functional proteins /
Okan, Osman Burak (2005) Glassiness and coupling of time scales in functional proteins /. [Thesis]
Folded proteins are functional at relatively elevated temperatures. Below ca. 190-220 K, proteins may still display the same average structure, but lack function due to the absence of large size fluctuations that increase nonlinearly with temperature. In this state, proteins are similar to polymers displaying glassy behavior, with their disordered, amorphous character and heterogeneous dynamics. We provide evidence that the onset of the relevant fluctuations at physiological temperatures occurs with the residue-wise alteration of the slow- nanosecond time scale- motions due to the activity along the envelope of the energy surface defining the folded protein, and the fast -pico second time scale- motions of the activity along the pockets decorating the folded- state envelope. We investigate this time window with spectral analysis methods to map all the relevant modes of fluctuations. Moreover, the temperature dependence of molecular motions are treated within the context of Fractional Brownian Dynamics. The analysis is based on data describing the relaxation phenomena governing the backbone dynamics derived from molecular dynamics simulations of three proteins in the temperature region 140-330K. The shifts in the weights of fundamental dynamical processes are displayed. Implications on controllability of function are discussed.
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