Flow-induced beta-hairpin folding of the glycoprotein Ibalpha beta-switch.

ABSTRACT: Flow-induced shear has been identified as a regulatory driving force in blood clotting. Shear induces beta-hairpin folding of the glycoprotein Ibalpha beta-switch which increases affinity for binding to the von Willebrand factor, a key step in blood clot formation and wound healing. Through 2.1-micros molecular dynamics simulations, we investigate the kinetics of flow-induced beta-hairpin folding. Simulations sampling different flow velocities reveal that under flow, beta-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 beta-switch from a loop to an elongated state. Lattice and freely jointed chain models i

SUBMITTER: Zou X 

PROVIDER: S-EPMC2920744 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature