Incipient structural and vibrational relaxation process of photolyzed carbonmonoxy myoglobin: statistical analysis by perturbation ensemble molecular dynamics method

Abstract

The incipient structural and vibrational energy relaxation process of photolyzed carbonmonoxy myoglobin was analyzed by the perturbation ensemble molecular dynamics (PEMD) method, in which many pairs of perturbed and unperturbed MD simulations are executed for ensemble-averaging to obtain statistically significant results by canceling out thermal fluctuations. First, we have shown that the experimentally reported anisotropic expansion can be detected within a picosecond after photolysis. The good agreement between the experimental and computational results indicates that the PEMD method can predict legitimately those changes driven by perturbations even if the changes might be subtle and smaller than thermal fluctuations. Second, the structural relaxation including the “clamshell rotation” in E and F helices was successfully analyzed. The high time resolution analysis has clarified the incipient structural dynamics on a subpicosecond timescale: the clamshell rotation starts at His64, Val68, and His93 following both the heme doming and the dissociated CO ligand collision. Third, the vibrational energy relaxation from the heme to the globin matrix is elucidated not only temporally but also spatially. This is the first “thorough” report of the spacetime-resolved excess kinetic energy redistribution of photolyzed MbCO in the globin matrix with a statistically significant precision, ±1 K. The incipient anisotropic vibrational relaxation occurs clearly within a picosecond in the direction perpendicular to the heme plane by the “through-bond” and “through-projectile” pathways, and the isotropic relaxation then follows by the “through-space” pathway. Finally, it is concluded that the PEMD method is a powerful tool to understand the incipient relaxation process driven by the perturbation.