From coarse‐grain to all‐atom: Toward multiscale analysis of protein landscapes

Multiscale methods are becoming increasingly promising as a way to characterize the dynamics of large protein systems on biologically relevant time-scales. The underlying assumption in multiscale simulations is that it is possible to move reliably between different resolutions. We present a method that efficiently generates realistic all-atom protein structures starting from the C(alpha) atom positions, as obtained for instance from extensive coarse-grain simulations. The method, a reconstruction algorithm for coarse-grain structures (RACOGS), is validated by reconstructing ensembles of coarse-grain structures obtained during folding simulations of the proteins src-SH3 and S6. The results show that RACOGS consistently produces low energy, all-atom structures. A comparison of the free energy landscapes calculated using the coarse-grain structures versus the all-atom structures shows good correspondence and little distortion in the protein folding landscape.