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Molecular Simulations Provide Insights into the Mechanics, but not the Time Scales, of Protein Motions under Equilibrium Conditions

Lin Liu, Angela Gronenborn, and Ivet Bahar


The same essential modes can be seen in long and short simulations, suggesting that functional motions are robustly defined by the shape of the global energy minimum.

Recent studies suggested that protein motions observed in molecular simulations are related to biochemical activities, although the computed time scales do not necessarily match those of the experimentally observed processes. The molecular origin of this conflicting finding is explored here for a test protein through a series of molecular dynamics simulations, covering three orders of magnitude in simulation time. Strikingly, increasing the simulation time leads to a uniform amplification of the sizes of the motion, while maintaining the same conformational mechanics. Residue fluctuations exhibit amplitudes of 1-2 A in the nanosecond simulations, while their average sizes increase by a factor of 4-5 in the microsecond regime. The mean-square displacements averaged over all residues (y) exhibit a power law dependence of the form y (infinity) x (^0.26) on the simulation time (x). The observed correlation times, on the other hand, increase linearly with the total length of the simulations.

Our results demonstrate that proteins possess robust preferences to undergo specific types of motions that already can be detected at short simulation times, provided that multiple runs are performed and carefully analyzed. On the other hand, the experimental time scale and absolute size of the motions cannot be extracted unambiguously from current state-of-the-art atomic simulations.


Related publication: Lin Liu, Gronenborn, AM, & Bahar, I. (submitted). Molecular simulations provide insights into the mechanics, but not the time scales, of protein motions under equilibrium conditions.