show that the nucleation of local α-helical domains is an activated process for both Based upon the 2D free energy analysis, we proceeded to contact-maps and secondary-structures analysis for CHARMM36m and CHARMM22* of BEMD, in comparison with results from CHARMM36m and CHARMM22* of PTMetaD-WTE (Fig. ). By focusing on residue-residue contacts with ~ 5 % frequencies, our analysis again reveals a sparse contact-map in which key contacts are mostly along the diagonal regions for all simulations. In respect of the off-diagonal regions, the four simulations show a lack of common residue-contacts. One exception is the Asn14-Ala24/Ser16-Lys22 domain of CHARMM36m BEMD. The contact-map of CHARMM36m BEMD displays prominent Asn14-Ala24 and Ser16-Lys22 contacts in this region, which is noticeably different from the other simulations within microsecond simulation length (Fig. ). At the same time, CHARMM36m BEMD explores a relatively lower number of α-helical structures, and a comparatively higher amount of β-strands in the domain of Asp18-to-Asn26, compared to the other method/force-field combinations (Fig. ).