Flow-induced β-hairpin folding of the glycoprotein ibα β-switch

Xueqing Zou, Yanxin Liu, Zhongzhou Chen, Gloria Ines Cárdenas-Jirón, Klaus Schulten

Research output: Contribution to journalArticlepeer-review


Flow-induced shear has been identified as a regulatory driving force in blood clotting. Shear induces β-hairpin folding of the glycoprotein Ibα β-switch which increases affinity for binding to the von Willebrand factor, a key step in blood clot formation and wound healing. Through 2.1-μs molecular dynamics simulations, we investigate the kinetics of flow-induced β-hairpin folding. Simulations sampling different flow velocities reveal that under flow, β-hairpin folding is initiated by hydrophobic collapse, followed by interstrand hydrogen-bond formation and turn formation. Adaptive biasing force simulations are employed to determine the free energy required for extending the unfolded β-switch from a loop to an elongated state. Lattice and freely jointed chain models illustrate how the folding rate depends on the entropic and enthalpic energy, the latter controlled by flow. The results reveal that the free energy landscape of the β-switch has two stable conformations imprinted on it, namely, loop and hairpin-with flow inducing a transition between the two.

Original languageEnglish (US)
Pages (from-to)1182-1191
Number of pages10
JournalBiophysical journal
Issue number4
StatePublished - Aug 9 2010

ASJC Scopus subject areas

  • Biophysics

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