FIG. 1.

Comparison between thermodynamic properties from MetaD and the HTMD adaptive sampling protocol. (a) Free-energy landscape of the MetaD simulations of the morphine-bound MOR as a function of CVs describing major conformational changes upon receptor activation (i.e., TM3-TM6 distance and NPxxYA RMSD from the MOR inactive crystal). Overlaid gray dots refer to the positions of the k-means centers of the free-energy landscape obtained from our previously published HTMD simulations of the morphine-induced MOR activation. (b) Correlation between the populations of each identified metastable region, i.e., the crystal-like active and inactive, intermediate I, and intermediate II regions, of the free-energy landscape of the morphine-induced MOR activation derived from MetaD or HTMD simulations.