Zhongzhou Chen, Jizhong Lou, Cheng Zhu, and Klaus Schulten. Flow induced structural transition in the β-switch region of glycoprotein Ib. Biophysical Journal, 95:1303-1313, 2008. (PMC: 2479615)

CHEN2008 The impact of fluid flow on structure and dynamics of biomolecules has recently gained much attention. In this paper we present a molecular dynamics algorithm that serves to generate stable water flow under constant temperature, for the study of flow-induced protein behavior. Flow simulations were performed on the 16-residue $\beta$-switch region of platelet glycoprotein Ib$\alpha$, for which crystal structures of its N-terminal domain alone and in complex with the A1 domain of von Willebrand factor have been solved. Comparison of the two structures reveals a conformational change in this region, which, upon complex formation, switches from an unstructured loop to a $\beta$-hairpin. Interaction between glycoprotein Ib and von Willebrand factor initiates platelet adhesion to injured vessel walls, and the adhesion is enhanced by blood flow. It has been hypothesized that the loop to $\beta$-hairpin transition in glycoprotein Ib$\alpha$ is induced by flow before binding to von Willebrand factor. The simulations revealed clearly a flow-induced loop $\rightarrow$ $\beta$-hairpin transition. The transition is dominated by the entropy of the protein, and is seen to occur in two steps, namely a dihedral rotation step followed by a side group packing step.



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