Notice of RetractionType 2B Mutations Destabilize vWF A1 Domain: A Molecular Dynamics Simulation Study

Notice of Retraction

After careful and considered review of the content of this paper by a duly constituted expert committee, this paper has been found to be in violation of IEEE´s Publication Principles.

We hereby retract the content of this paper. Reasonable effort should be made to remove all past references to this paper.

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Adhesion of platelets to subendothelium of blood vessels at sites of vascular injury under high shear conditions is mediated by interaction between platelet receptor glycoprotein Ibα (GPIbα) and Al domain of von Willebrand factor (VWF). Gain-of-function mutations in Al domain can cause type 2B von Willebrand disease which associates with excessive bleeding. To illustrate how type 2B mutations activate Al, we use molecular dynamics (MD) simulations to investigate in atomic details the effects of three type 2B mutations R543Q, I546V and R687E on the Al domain. At physiological temperature, these mutations increase the radius of gyration and solvent accessible surface area of Al, by enforcing the N-terminus to detach from the rest part, and consequently destabilize the Al domain. The regions that the mutations affect mainly involve β2-β3 turn, β3 strand, β3-α2 loop, and α2 helices. The results help us to understand the affinity regulation mechanism between Al and Gplbα by type 2B mutations.