Energy Transport Pathways in Proteins: A Non-equilibrium Molecular Dynamics Simulation Study.

To facilitate the observation of biomolecular energy transport in real time and with single-residue resolution, recent experiments by Baumann et al. ( Angew. Chem. Int. Ed. 2019 , 58 , 2899 , DOI: 10.1002/anie.201812995 ) have used unnatural amino acids β-(1-azulenyl)alanine (Azu) and azidohomoalanine (Aha) to site-specifically inject and probe vibrational energy in proteins. To aid the interpretation of such experiments, non-equilibrium molecular dynamics simulations of the anisotropic energy flow in proteins TrpZip2 and PDZ3 domains are presented. On this account, an efficient simulation protocol is established that accurately mimics the excitation and probing steps of Azu and Aha. The simulations quantitatively reproduce the experimentally found cooling times of the solvated proteins at room temperature and predict that the cooling slows by a factor 2 below the glass temperature of water. In PDZ3, vibrational energy is shown to travel from the initially excited peptide ligand via a complex network of inter-residue contacts and backbone transport to distal regions of the protein. The supposed connection of these energy transport pathways with pathways of allosteric communication is discussed.