WT CD28 can adopt a stable conformation that would allow bivalent binding.

<p>MD simulations were run with WT CD28 starting from a rotated dimer orientation predicted from the simulations starting from the CTLA-4 dimer orientation. (<b>A</b>) The RMSD with respect to the initial conformation for three independent trajectories indicate that these dimer conformers are very stable. (<b>B</b>) When CD80 molecules were docked onto the conformations, there was no surface buried between the ligands, indicating that all conformations were bivalent. A representative bivalent conformation of CD28 (green) with docked CD80 molecules (cyan) is shown to illustrate the CD28 dimer (<b>C</b>) and in a rotated view to show the orientation of the docked CD80 molecules (<b>D</b>).</p>