Picosecond fluctuating protein energy landscape mapped by pressure–temperature molecular dynamics simulation
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.
Additional Information© 2007 the National Academy of Sciences. Contributed by Ahmed H. Zewail, August 30, 2007 (sent for review June 28, 2007). Published online on October 23, 2007, 10.1073/pnas.0708199104. This work was supported by the Physical Biology Center for Ultrafast Science and Technology. L.M. acknowledges support from a Deutsche Physikalische Gesellschaft/Deutsche Forschungsgemeinschaft fellowship to visit Japan before joining the group at The California Institute of Technology. Author contributions: L.M., J.C.S., A.K., and A.H.Z. performed research; and L.M., J.C.S., A.K., and A.H.Z. wrote the paper. The authors declare no conflict of interest.
Published - MEIpnas07.pdf