Paper Citing NAMD - Abstract
Zou, Xueqing; Liu, Yanxin; Chen, Zhongzhou; Ines Cardenas-Jiron, Gloria; Schulten, Klaus
Flow-Induced beta-Hairpin Folding of the Glycoprotein Ib alpha beta-Switch
BIOPHYSICAL JOURNAL, 99:1182-1191, AUG 18 2010
Flow-induced shear has been identified as a regulatory driving force in blood clotting. Shear induces beta-hairpin folding of the glycoprotein Ib alpha 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-mu s 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 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 beta-switch has two stable conformations imprinted on it, namely, loop and hairpin with flow inducing a transition between the two.
