All-atom simulation of the HET-s prion replication
Fig 4
Reaction pathways in HET-s rungs formation.
The heat-maps represent the negative logarithm of the probability density calculated from the SCPS reactive paths at different iterations, as a function of the RMSD from the target structure of the N- and T-terminal rungs, i.e. -ln[P(RMSDCT-Rung, RMSDNT-Rung)]. A. Graphs relative to trajectories propagating from the fibril N-terminus. B. Graphs relative to the trajectories propagating from the fibril C-terminus. In both cases, a prominent pathway, consisting of the consecutive formation of rungs starting at the fibril end, begins to appear in the rMD generated trajectories. However, the rMD algorithm also yields pathways with cooperative or inverted rung formation. These alternative events are disappeared after a single SCPS iteration. Of note, a second SCPS iteration does not produce a consistent change in the free energy landscape in both A and B, indicating the convergence of the algorithm.