The von Willebrand factor (VWF), a multimeric plasma glycoprotein, binds to the platelet glycoprotein (GPIb alpha) to initiate the process of primary hemostasis as a response to blood flow alteration in the site of vascular injury. The GPIb alpha binding site located on the A1 domain of VWF is exposed during the activation of the VWF multimer when it changes from a coiled form to a thread-like, extended form. Though experimental studies have demonstrated that the autoinhibitory module (AIM) connected to the N-/C-termini of the A1 domain is a regulator of VWF activity, the molecular mechanism underlying the regulation of A1-GPIb alpha binding remains unclear. We modeled the structures of the A1 domain having full-length N-terminal AIM (NAIM) and C-terminal AIM (CAIM) with different types of O-linked glycans. The conventional and steered molecular dynamics simulations were conducted to investigate the dynamics of the AIM and O-glycans under different conditions and elucidate how they affect the binding of GPIb alpha. Our results indicate that the NAIM alone with no glycan is sufficient to shield the GPIb alpha binding site under static conditions. However, when the AIM is unfolded with external forces applied, the O-glycans on both NAIM and CAIM increase the shielding of the binding site. These findings suggest a potential mechanism by which the AIM and O-glycans regulate the interaction of the VWF A1 domain and GPIb alpha.