Fig. 2
The backbone structure of heteronemin and estradiol and the docked binding modes of several ligands are shown with the RGD-recognition site of integrin αvβ3 (PDB entry 1L5G) [95]. Docking was carried out by AutoDock Vina software [96] in the RGD domain pocket. The grid map function in Auto-Dock 4.0 was used to define the interaction space of protein and ligand in the binding pocket. For ligand binding to the RGD domain site, a grid box of size 45 × 45 × 45 points was established in the x, y, and z directions, with the grid centers set at x = 19, y = 44, and z = 44. The docking pose results of the ligands were prepared and visualized with the graphic PyMOL (v. 1.3) program. A The chemical structures of integrin αvβ3 ligand include cyclic RGD (cRGD), thyroxine (T4), resveratrol (RSV), and estradiol (E2). Heteronemin (yellow) and estradiol (orange) show similar skeletons as presented in the black bold bond and three-dimensional superimposition. B The crystal structure of the integrin αvβ3 and cRGD complex is shown on the protein surface. Integrin αv subunit (green), β3 subunit (cyan), and cRGD peptide (magenta) are indicated by color. C Thyroxine (T4), resveratrol (RSV), and estradiol (E2) are performed in red, blue, and orange, respectively. The superimposition shows similar orientations of the binding site between the cRGD (magenta stick) and resveratrol (blue stick). D Predicted bound conformation of T4 (red), RSV (blue) and E2 (orange). The projections are according to previous publications [23, 90]. E According to the previous publication [23], the schematic representation is shown in three major pockets, including the thyroid hormone pocket, the resveratrol pocket, and the steroid pocket