Trajectory and Cluster Analyses. Trajectory analysis and sorting out the target temperatures were done with the CPPTRAJ module of AmberTools 18 . Analyses of the T-REMD were done at the 299.5 K replica, closest to the room temperature. Cluster analysis was done using the average-linkage hierarchical agglomerative method . Heavy atoms of 2×2 GG/GG loop residues were used in the cluster analyses with a root-mean-square deviation (RMSD) of 1.2 Å.