Modeling of selected mutations on αIIbβ3 structure. (A) Schematic representation of αIIbβ3 in open conformation. (B) Computer-drawn ribbon diagram of αIIb (blue, cap in light blue) and β3 (green) headpieces in open conformation; Arg261 (yellow spheres) in β3 is shown as a space-filling model.²⁹  A 90° rotation of the αIIb β-propeller (C) and the β3 βΑ I-like domain (D) exposes the surfaces normally in contact with each other. (D) Amino acids (orange sticks) affected by mutations giving variant forms (Table 1). (E) Metal coordination sites in the SyMBS (yellow), MIDAS (orange), and ADMIDAS (brown) domains; N atoms are blue and O atoms are red; Ca²⁺ (gray spheres), Mg²⁺ (pale blue spheres), and water (blue small spheres). Metal coordination and hydrogen bonds are shown as dashed lines; Asp119 (orange) and the mutated Asn (red) are superimposed. E220 contributes to both SyMBS and MIDAS, although colored yellow. (F) Electrostatic potential surfaces of the β1 domain, with views (small windows) of charge changes caused by the 3 highlighted mutations (for clarity, the corresponding mutation sites are indicated on the whole image by white arrows). (G) Ribbon diagrams of I-EGF3 (yellow) and I-EGF4 (green) domains of β3. Selected disulfides are illustrated with Cys549 (orange stick) interacting with Cys558 (yellow stick), and Cys560 (orange stick) bonded to Cys583 (green stick).⁵⁵  Mutations (G₁, G₂) are shown as graphical red stick representations in small windows; graphical “bumps” (red discs) indicate steric interactions caused by the Arg549 and Arg560 substitutions. (H) Ribbon diagrams of the cytoplasmic domains of αIIbβ3. Shown is the ionic interaction of Arg995 of αIIb (pale blue stick, positively charged) and Asp723 of β3 (pale green stick, negatively charged). (H₁-H₂) Amino acid changes in the salt link in cytoplasmic domain variants (Table 1). (H1) Replacement of Arg995 of αIIb by Gln modifies the ionic interaction with a hydrogen bond of moderate force with respect to the distance and angle formed by the 3 atoms engaged in the link. (H2) Substitution of Asp723 of β3 by His causes the complete loss of the interaction with Arg995. (I) Ser752 (orange stick) of β3 with (I₁) showing images of the electrostatic potential surface changes induced by the mutation Ser752Pro. Models were obtained using the PyMol Molecular Graphics System Version 1.3 (Schrödinger LLC; www.pymol.org) and 2vdo, 3fcs, and 2knc pdb files for crystal structure of αIIb and/or β3 subunits. Amino acid changes are rotamer incorporated from the Dunbrack Backbone library with the maximum probability. Electrostatic potential surface calculation and visualization were obtained with the Adaptive Poisson-Boltzmann Solver software incorporated in PyMol Version 1.3 software.¹⁰⁴