TY - JOUR
T1 - Flow-induced structural transition in the β-switch region of glycoprotein Ib
AU - Chen, Zhongzhou
AU - Lou, Jizhong
AU - Zhu, Cheng
AU - Schulten, Klaus
N1 - Funding Information:
This work was funded by the National Institutes of Health grant No. P41-RR05969 (K.S.) and HL091020 (C.Z.). The authors gladly acknowledge supercomputer time provided by the Pittsburgh Supercomputing Center and the National Center for Supercomputing Applications via Large Resources Allocation Committee grant No. MCA93S028.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - The impact of fluid flow on structure and dynamics of biomolecules has recently gained much attention. In this article, 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 β-switch region of platelet glycoprotein Ibα, 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 β-hairpin. Interaction between glycoprotein Ibα 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 β-hairpin transition in glycoprotein Ibα is induced by flow before binding to von Willebrand factor. The simulations revealed clearly a flow-induced loop→β-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.
AB - The impact of fluid flow on structure and dynamics of biomolecules has recently gained much attention. In this article, 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 β-switch region of platelet glycoprotein Ibα, 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 β-hairpin. Interaction between glycoprotein Ibα 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 β-hairpin transition in glycoprotein Ibα is induced by flow before binding to von Willebrand factor. The simulations revealed clearly a flow-induced loop→β-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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U2 - 10.1529/biophysj.108.132324
DO - 10.1529/biophysj.108.132324
M3 - Article
C2 - 18441028
AN - SCOPUS:51049096157
VL - 95
SP - 1303
EP - 1313
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 3
ER -