FIGURE 7.

The β1-α1 loop regulates the stability of the force-bearing Asp^RGD-MIDAS bond. A, the force-bearing bond between Oδ-2 of Asp^RGD (black) and the MIDAS ion (red) occurs at the top of the β1-α1 loop, shown in green, schematic, and transparent surface representations. When the Asp^RGD and Tyr¹²² hydrogen bond is formed (dashed line), the β1-α1 loop packs in tightly with the Asp^RGD side chain. Water molecules within 5 Å of the Oδ-2 atom are shown in blue van der Waals representation. B, when the bond between Asp^RGD–Tyr¹²² was formed under force, as evident from the trace of the heavy atom distance (right side, traced in black), shielding of force-bearing Oδ-2 atom from attack by free water molecules was increased (left side, traced in blue). Water contact events to the Oδ-2 atom were counted for each time step (picosecond intervals) by identifying the number of water molecules within 3 Å of the Oδ-2 atom. C, when the Asp^RGD–Tyr¹²² bond was already formed under force, this bond remained formed (right side, black trace) and the Oδ-2 atom remained shielded from attack by water molecules (left side, blue trace). When instead both of the Oδ-1 and Oδ-2 atoms coordinated the MIDAS ion (D) and the Asp^RGD–Tyr¹²² bond did not form (E, right side), the Asp^RGD atom that forms the force-bearing bond with the MIDAS ion, Oδ-2, was subject to a relatively higher level of water molecule attacks.