Molecular dynamics simulations and linear response theories jointly describe biphasic responses of myoglobin relaxation and reveal evolutionarily conserved frequent communicators

In this study, we provide a time-dependent (td-) mechanical model, taking advantage of molecular dynamics (MD) simulations, quasiharmonic analysis of MD trajectories and td-linear response theories (td-LRT) to describe vibrational energy redistribution within the protein matrix. The theoretical description explains the observed biphasic responses of specific residues in myoglobin to CO-photolysis and photoexcitation on heme. The fast responses are found triggered by impulsive forces and propagated mainly by principal modes <40 cm -1 . The predicted fast responses for individual atoms are then used to study signal propagation within protein matrix and signals are found to propagate ∼ 8 times faster across helices (4076 m/s) than within the helices, suggesting the importance of tertiary packing in proteins’ sensitivity to external perturbations. We further develop a method to integrate multiple intramolecular signal pathways and discover frequent “communicators”. These communicators are found evolutionarily conserved including those distant from the heme.