TY - JOUR
T1 - Flow-induced β-hairpin folding of the glycoprotein ibα β-switch
AU - Zou, Xueqing
AU - Liu, Yanxin
AU - Chen, Zhongzhou
AU - Cárdenas-Jirón, Gloria Ines
AU - Schulten, Klaus
N1 - This work has been supported by the National Institutes of Health (under grant No. P41-RR005969) and Cell Mechanics (under grant No. R01 GM073655), as well as by the China Scholarship Council. G.I.C.-J. thanks Project FONDECYT grant No. 1060203/CHILE and Vicerrectoría de Investigación y Desarrollo/Universidad de Santiago de Chile for financial support. The authors gladly acknowledge supercomputer time provided via Large Resources Allocation Committee grant No. MCA93S028, and the Turing Xserve Cluster operated by Computational Science and Engineering at the University of Illinois.
PY - 2010/8/9
Y1 - 2010/8/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77958165857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958165857&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2010.05.035
DO - 10.1016/j.bpj.2010.05.035
M3 - Article
C2 - 20713002
AN - SCOPUS:77958165857
SN - 0006-3495
VL - 99
SP - 1182
EP - 1191
JO - Biophysical journal
JF - Biophysical journal
IS - 4
ER -