Forced extension of P-selectin construct using steered molecular dynamics |
| |
Authors: | Shouqin?Lü Email author" target="_blank">Long?MianEmail author |
| |
Institution: | e-mail: mlong@
imech.ac.cn |
| |
Abstract: | P-selectin, a 70-nm-long cellular adhesive molecule, possesses elastic and extensible properties when neutrophils roll over
the activated endotheliam of blood vessel in inflammatory reaction. Transient formation and dissociation of P-selectin/ligand
bond on applied force of blood flow induces the extension of P-selectin and relevant ligands. Steered molecular dynamics simulations
were performed to stretch a single P-selectin construct consisting of a lectin (Lec) domain and an epithelial growth factor
(EGF)-like domain, where P-selectin construct was forced to extend in water with pulling velocities of 0.005–0.05 nm/ps and
with constant forces of 1000–2500 pN respectively. Resulting force-extension profiles exhibited a dual-peak pattern on various
velocities, while both plateaus and shoulders appeared in the extension-time profiles on various forces. The force or extension
profiles along stretching pathways were correlated to the conformational changes, suggesting that the structural collapses
of P-selectin Lec/EGF domains were mainly attributed to the burst of hydrogen bonds within the major β sheet of EGF domain
and the disruptions of two hydrophobic cores of Lec domain. This work furthers the understanding of forced dissociation of
P-selectin/ligand bond. |
| |
Keywords: | force extension P-selectin steered molecular dynamics |
本文献已被 CNKI 万方数据 SpringerLink 等数据库收录! |
| 点击此处可从《中国科学通报(英文版)》浏览原始摘要信息 |
| 点击此处可从《中国科学通报(英文版)》下载免费的PDF全文 |