Simulation of electron paramagnetic resonance spectra of spin-labeled molecules from replica-exchange molecular dynamics.

We report a general approach for the simulation of the electron paramagnetic resonance (EPR) spectra of spin labels attached to peptides and proteins directly from replica-exchange molecular dynamics (REMD) trajectories. Conventional MD trajectories are generally inadequate for the prediction of EPR line shapes since the label can become trapped in one or more of a set of rotameric states, thus preventing both conformational sampling and accurate estimates of the exchange rates between different rotamers. The advantage of using REMD is its ability to provide both efficient conformational sampling and kinetic information for spin-label dynamics. Our approach is illustrated with spin-labeled peptide. This approach to REMD-EPR simulation paves the way for the wider application of MD modeling to the simulation and interpretation of EPR spectra of spin-labeled molecules.