Redox-Dependent Vibrational Energy Flow in Amicyanin Revealed by Molecular Dynamics Simulations.

Understanding how redox events influence intraprotein energy flow is essential for elucidating the dynamical basis of biological electron transfer. Here, we investigate redox-dependent vibrational energy redistribution in the type I copper protein amicyanin using atomistic molecular dynamics simulations combined with time-correlation and cross-correlation analyses of residue-resolved energy fluctuations. Energy-difference time series constructed for the Cu+ and Cu2+ states were used to characterize vibrational spectra, dynamical couplings, and ensemble-based energy-transfer pathways originating from the metal coordination sphere. Our analysis reveals that vibrational energy injected at the copper center propagates through a small subset of highly probable residue pathways that form a distributed communication network rather than a single dominant channel. Top-ranked pathways exhibit nearly identical efficiencies in the reduced and oxidized states, with representative pathway scores of ∼2.6 × 10-2 for both Cu+ and Cu2+. Across the ensemble of major pathways, efficiency ratios lie in the narrow range 0.95-1.02, indicating that changes in copper oxidation state modulate the amplitude of energetic fluctuations while preserving the underlying routes of energy propagation. Extension of this analysis to the amicyanin-cytochrome c551i interface reveals coherent interprotein coupling mediated by both residue-residue interactions and dynamically structured interfacial water. Hydrogen-bond lifetime analysis demonstrates that interfacial water exhibits confined, heterogeneous dynamics characteristic of protein-protein interfaces, providing a dynamical bottleneck that supports energy redistribution across the complex. Together, these results demonstrate that amicyanin employs a robust, preorganized vibrational communication network conserved under redox cycling, offering a mechanistic framework for reliable long-range dynamical coupling between local redox chemistry and global protein response.