Effects of Deformation Rate on the Unbinding Pathway of the MMP8-Aggrecan_IGD Complex in Cartilage  

作　　者：Deng Li Shuwei Chang 

机构地区：[1]Department of Civil Engineering,National Taiwan University,Taipei 10617,Taiwan

出　　处：《Computer Modeling in Engineering & Sciences》2019年第8期305-318,共14页工程与科学中的计算机建模（英文）

摘　　要：Mechanical force plays a critical role in the remodeling and degradation of cartilage tissues.The cartilage tissue generates,absorbs,and transmits mechanical force,enabling specific biological processes in our body.A moderate intensity mechanical force is necessary for cartilage tissue remodeling and the adaptation of biomechanical properties,but a high intensity mechanical force can lead to pathological degradation of cartilage tissue.However,the molecular mechanism of cartilage degradation is still unclear.We use full atomistic simulations with SMD simulations to investigate whether the magnitude of mechanical force affects the unbinding pathway of the MMP8-Aggrecan_IGD complex.We find that when the pulling velocity is slow,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is higher,and a three-step unbinding pathway is observed.On the other hand,when the pulling velocity is fast,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is lower,and a two-step unbinding pathway is observed.Our results help us to understand how the magnitude of the mechanical force affects the unbinding pathway of the enzyme-ligand complex in cartilage tissue at the molecular level.

关 键 词：Mechanical FORCE steered molecular dynamics(SMD) unbinding PATHWAY potential of mean force(PMF) 

分 类 号：TG1[金属学及工艺—金属学]