(a) The heavy-atom RMSD of the 10 amino acids from the BL2 loop (Gly262–Gly272) over 22 ns of total simulation time, starting from the bound closed form of the loop. The loop assumes the open state around 5, 10–13.5, 14.5, 18, and 19.5–22 ns. The RMSD profile of the bound form of the protein over the simulation with respect to the apo X-ray structure is shown in blue, whereas the RMSD with respect to the GRL0617 ligand-bound X-ray structure is shown in magenta. (b) The ϕ–Ψ dihedral of the peptide bond between Tyr269–Gln270 inverts from the starting closed GRL0617-bound conformation (ϕ of Gln270, 72.2; Ψ of Tyr269, 124.9) to the open unbound state (ϕ of Gln270, −74.9; Ψ of Tyr269, −58.4) during the final 2.5 ns of simulation time. aMD on the 10 loop residues successfully sampled the ϕ–Ψ dihedral rotation from one state to another. The ϕ angle of residue Gln270 is shown in black, and the Ψ of Tyr269 is shown in red. (c and d) The dihedral torsion changes of two neighboring loop residues, Gly267 and Gly272, which eventually lead to the –Tyr–Gln–peptide bond inversion. The Ψ angles (shown in red) of Gly267 as seen in (c) and of Gly272 as seen in (d) (shown in red) start increasing after 17 ns, which may allow the decrease of the ϕ of Gln270, and then around 19.5 ns, the Ψ of Tyr269 starts decreasing until the Tyr–Gln peptide bond assumes the apo open loop conformation. The ϕ angles of the hinging glycine residues are shown in black and the Ψ angles are shown in red.