Temperature effects on protein motions: A molecular dynamics study of RNase-Sa

The dynamics of the enzyme ribonuclease-Sa as a function of temperature has been explored through a series of molecular dynamics simulations. Long-ran ge expansion and short-range contraction of the structure lends the protein a solidlike core and a liquidlike exterior as the temperature is increased . The trend in magnitudes of fluctuations of atoms are biphasic across the 150-200K region and are increasingly non-Brownian in character as the tempe rature is increased. The mobility of solvent molecules is much higher than the protein atoms, even though the solvent mobility displays behavior which is dampened relative to behavior in bulk water. The region of the active s ite that binds the base of the nucleotide ligand shows low plasticity relat ive to regions that interact with the sugar-phosphate part. This suggests t hat the enzyme is preorganized dynamically: regions with low plasticity con fer specificity while the more flexible regions have the fluidity to facili tate energetically inexpensive conformational rearrangements such as those required to achieve the transition state. Below 200K the dynamics are chara cterized by low amplitude harmonic motions that involve concerted motions t hat involve small groups of atoms. Above 200K, the dynamics are dominated b y large amplitude anharmonic motions which involve long-range correlations including breathing and twisting modes such as those required for ligand bi nding/release/activation. The temperature-dependent transition in the chara cter of the dynamics at similar to 200K reflects the ease with which the sy stem hops among barriers giving rise to enhanced diffusion across phase spa ce. This enhanced plasticity is catalyzed by a significant increase in the mobility of solvent water molecules and the associated increase in frequenc y of different hydrogen bond arrangements and may facilitate the onset of s ignificantly enhanced functionality above the transition temperature.