Fig. 7: Simulated partial unbinding and binding of secretin using well-tempered metadynamics simulations.
From: Structure and dynamics of the active Gs-coupled human secretin receptor
a Overview of the simulation displayed in Video 3. b Heat map of the interaction of secretin residues 2 (left panel), 5 (left middle panel), 6 (right middle panel), and 7 (right panel), equivalent to the positions of cysteine substitution in cross-linking studies, with the SecR core during simulations. The position of the secretin residue in the cryo-EM structure is displayed in green cpk representation, with the rest of the peptide displayed in transparent light gray ribbon format. The receptor core is shown in surface representation colored according to frequency of interactions during the simulation. c Speculative schematic illustrating a potential binding intermediate that could account for observed cysteine-cross-linking data prior to the peptide reaching its metastable position observed in the active, G protein-coupled receptor structure.
