Structural Transition of Solvated H-Ras/GTP Revealed by Molecular Dynamics Simulation and Local Network Entropy

The state transitions of solvated H-Ras protein with GTP were theoretically analyzed through molecular dynamics (MD) simulations. To accelerate the structural changes associated with the locations of two switch regions (I and II), the Parallel Cascade Selection MD (PaCS-MD) method was employed in this study. The interconversions between the State 1 and State 2 were thus studied in atomic details, leading to a reasonable agreement with experimental observations and consequent scenarios concerning the transition mechanism that would be essential for the development of Ras inhibitors as anti-cancer agents. Furthermore, the state-transition-based local network entropy (SNE) was calculated for the transition process from State 1 to State 2, by which the temporal evolution of information entropy associated with the dynamical behavior of hydrogen bond network composed of hydration water molecules was described. The calculated results of SNE thus proved to provide a good indicator to detect the dynamical state transition of solvated Ras protein system (and probably more general systems) from a viewpoint of nonequilibrium statistical thermodynamics.