Figure 1.
Free-energy landscape of PrP-H1. The surface is drawn as a 3D curve as well as a projection on the CV plane. For each basin, representative conformations are drawn by means of the Cα trace (red, N-terminus; blue, C-terminus). The energy isolines are plotted with 1 kJ/mol of spacing and color-coded for better visibility, with the lowest level (blue) corresponding to −28 kJ/mol. This is the case of a significantly populated basin among the RC conformations that is centered at H-bond values of ∼0 and rgyr-values of ∼0.8 nm. This basin, which is very narrow in this projection, hosts the 13.4% of the reweighted population of the sampling and has a free-energy value of −35.6 kJ/mol. The sampling was performed by means of PT-MetaD (17), using the PLUMED (59) plugin interfaced with GROMACS (60). The PT-MetaD sampling involved 50 replicas ranging from 283 K to 471 K. The calculations were extended for 48 ns, and the reconstructed FES was averaged over the converged part of the simulation.