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We examine vibrational energy flow in dehydrated and hydrated villin headpiece subdomain HP36 by master equation simulations. Transition rates used in the simulations are obtained from communication maps calculated for HP36. In addition to energy flow along the main chain, we identify pathways for energy transport in HP36 via hydrogen bonding between residues quite far in sequence space. The results of the master equation simulations compare well with all-atom non-equilibrium simulations to about 1 ps following initial excitation of the protein, and quite well at long times, though for some residues we observe deviations between the master equation and all-atom simulations at intermediate times from about 1-10 ps. Those deviations are less noticeable for hydrated than dehydrated HP36 due to energy flow into the water. [ABSTRACT FROM AUTHOR]

Based on a given time series, the data-driven Langevin equation (dLE) estimates the drift and the diffusion field of the dynamics, which are then employed to reproduce the essential statistical and dynamical features of the original time series. Because the propagation of the dLE requires only local information, the input data are neither required to be Boltzmann weighted nor to be a continuous trajectory. Similar to a Markov state model, the dLE approach therefore holds the promise of predicting the long-time dynamics of a biomolecular system from relatively short trajectories which can be run in parallel. The practical applicability of the approach is shown to be mainly limited by the initial sampling of the system's conformational space obtained from the short trajectories. Adopting extensive molecular dynamics simulations of the unfolding and refolding of a short peptide helix, it is shown that the dLE approach is able to describe microsecond conformational dynamics from a few hundred nanosecond trajectories. In particular, the dLE quantitatively reproduces the free energy landscape and the associated conformational dynamics along the chosen five-dimensional reaction coordinate. [ABSTRACT FROM AUTHOR]

A local perturbation of a proteinmay lead to functional changesat some distal site. An example is the PDZ2 domain of human tyrosinephosphatase 1E, which shows an allosteric transition upon bindingto a peptide ligand. Recently Buchli et al. presented a time-resolvedstudy of this transition by covalently linking an azobenzene photoswitchacross the binding groove and using a femtosecond laser pulse thattriggers the cis–trans photoisomerization of azobenzene. Toaid the interpretation of these experiments, in this work seven microsecondruns of all-atom molecular dynamics simulations each for the wild-typePDZ2 in the ligand-bound and -free state, as well as the photoswitchableprotein (PDZ2S) in the cis and trans states of the photoswitch, inexplicit water were conducted. First the theoretical model is validatedby recalculating the available NMR data from the simulations. By comparingthe results for PDZ2 and PDZ2S, it is analyzed to what extent thephotoswitch indeed mimics the free-bound transition. A detailed descriptionof the conformational rearrangement following the cis–transphotoisomerization of PDZ2S reveals a series of photoinduced structuralchanges that propagate from the anchor residues of the photoswitchvia intermediate secondary structure segments to the C-terminus ofPDZ2S. The changes of the conformational distribution of the C-terminalregion is considered as the distal response of the isolated allostericprotein. [ABSTRACT FROM AUTHOR]

Computational studies of vibrational energy flow in biomolecules have to date mapped out transport pathways on a case-by-case basis. To provide a more general approach, we derive scaling rules for vibrational energy transport in a globular protein, which are identified from extensive nonequilibrium molecular dynamics simulations of vibrational energy flow in the villin headpiece subdomain HP36. We parametrize a master equation based on inter-residue, residue-solvent, and heater-residue energy-transfer rates, which closely reproduces the results of the all-atom simulations. From that fit, two scaling rules emerge, one for energy transport along the protein backbone which relies on a diffusion model and another for energy transport between tertiary contacts, which is based on a harmonic model. Requiring only the calculation of mean and variance of relatively few atomic distances, the approach holds the potential to predict the pathways and time scales of vibrational energy flow in large proteins.