Structural Stability of Force-Regulated FLNa-Ig21/αⅡbβ3-CT Complexes by Molecular Dynamics Simulation
10.16156/j.1004-7220.2024.01.007
- VernacularTitle:力调控FLNa-Ig21/αⅡbβ3-CT复合物结构稳定性的分子动力学研究
- Author:
Jianfang REN
1
,
2
;
Yichong LUO
;
Jianhua WU
;
Ying FANG
Author Information
1. 华南理工大学 生物科学与工程学院
2. 生物力学所, 广州 510006
- Keywords:
platelet integrin;
molecular dynamics(MD)simulation;
unfolding pathway;
mechanical strength;
mechanical regulation mechanism
- From:
Journal of Medical Biomechanics
2024;39(1):46-54
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αⅡbβ3-CT complex and the regulation mechanism.Methods The FLNa-Ig21/αⅡbβ3-CT crystal structures were taken from the PDB database.The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations.Results During the equilibration,the survival rate of most salt bridge and hydrogen bonds was below 0.5,and the interactions between FLNa-Ig21 and αⅡbβ3-CT was relatively weak.During stretching at a constant velocity,the complex could withstand a tensile force of 70-380 pN,and its mechanical strength depended on the force-induced dissociation path.Under a constant force of 0-60 pN,the complexes exhibited a slipping-bond trend,and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αⅡbβ3 integrin.Conclusions The force-induced allostery of αⅡbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αⅡbβ3-CT.After breaking through the 20 pN threshold,force positively regulated the activation of αⅡbβ3 integrin.These results provide insights into the molecular mechanism of αⅡbβ3 activation and the development of related targeted drugs.
