The Effect Of Solvent Temperature On Dynamics Of Serine Protease Proteinase K

The dynamics of proteins, which are essential for their biological functions, originate from atomic thermal motions that are determined by the temperatures of biologically relevant environments. To obtain the detailed information about the effects of the solvent temperatures on protein dynamics, a series of molecular dynamics (MD) simulations of serine protease proteinase K in explicit solvent with the solute and the solvent coupled to different temperatures (P180/S180, P300/S180, P180/S300, and P300/S300, where P and S refer to the protein and solvent, respectively, and180and300are temperatures in Kelvin), have been performed. Comparative analyses of the simulated trajectories demonstrate that the internal flexibility and mobility of proteinase K are strongly dependent on the solvent temperatures but weakly on the protein temperatures. The enhanced solvent temperature greatly promotes the functionally relevant collective motions (or large-scale concerted motions) and enlarges the sampled conformational spaces of the protein, mainly through increasing the displacement magnitude and extending the sampled range of the surface-exposed residues/regions that are directly involved in interactions with the solvent. The free energy landscapes (FELs) at the high solvent temperatures exhibit a more rugged surface, wider spanning range, and higher minimum free energy level than do those at low solvent temperatures, implying that the high solvent temperature increases the conformational diversity and conformational entropy while reducing the thermostabilility of the protein. Comparison between the dynamic hydrogen-bonding numbers reveals that the high solvent temperatures intensify the competitive hydrogen-bonding interactions between the solvent and the protein atoms, and this in turn exacerbates the competitive HB interactions between protein internal atoms, thus increasing the conformational flexibility and facilitating the collective motions of the protein. Our simulations complement previous experimental and theoretical studies, demonstrating that the solvent mobility is a dominant factor in determining the functionally important protein motions.