Homology model of VWF A2 domain showing Tyr1584Cys mutation and common polymorphisms. (A) Homology model of the VWF A2 domain was developed, based on the crystallographic structures of homologous domains from the integrins α1-β1, α2-β1, αL, and αM and from the VWF A1 and A3 domains. Tyr1584 was replaced with cysteine on alpha helix 4, and a molecular dynamic simulation was performed to assess the effect of this substitution on protein structure. No significant structural changes were observed. The reactive thiol group on the side chain of Cys1584 (indicated as a yellow ball) is 100% exposed to solvent. Common polymorphisms are also labeled in the figure.