Picosecond fluctuating protein energy landscape mapped by pressure–temperature molecular dynamics simulation

Abstract

Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure. In contrast, vibrations within substates stiffen with pressure, due to increased curvature of the local harmonic potential in which the atoms vibrate. The application of pressure is also shown to selectively increase the damping of the anharmonic, low-frequency collective modes in the protein, leaving the more local modes relatively unaffected. The critical damping frequency, i.e., the frequency at which energy is most efficiently dissipated, increases linearly with pressure. The results suggest that an invariant description of protein energy landscapes should be subsumed by a fluctuating picture and that this may have repercussions in, for example, mechanisms of energy dissipation accompanying functional, structural, and chemical relaxation.

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