FIGURE 5.

The occupancies of the salt‐bridging interactions between the H‐loop and the α14 helix residues and the participating residues are highlighted. The occupancies of the salt‐bridging interactions are shown for the (a) six independent simulations of the apo form, (b) six independent simulations of the evodiamine‐bound form, and (c) four independent simulations of the avanafil‐bound form. (d) The salt‐bridging interactions (black dotted lines) between the α14 helix (green), the H‐loop (yellow), and the M‐loop (purple) are shown. The C _α atoms of the acidic residues (red spheres) and of the basic residues (blue spheres) are shown. These interactions stabilize the structural motifs surrounding the catalytic site and mediate the inward and the outward conformational transition of the α14 helix. (e) The color coded conservation scores of the residues of the H‐loop and the α14 helix obtained from the Consurf webserver (Ashkenazy et al., 2016; Chorin et al., ²⁰¹⁹) are also depicted on the PDE5 structure.