MD Simulations on a Well-Built Docking Model Reveal Fine Mechanical Stability and Force-Dependent Dissociation of Mac-1/GPIbα Complex.

ABSTRACT: Interaction of leukocyte integrin macrophage-1 antigen (Mac-1) to platelet glycoprotein Ibα (GPIbα) is critical for platelet-leukocyte crosstalk in hemostasis and inflammatory responses to vessel injuries under hemodynamic environments. The mechano-regulation and its molecular basis for binding of Mac-1 to GPIbα remain unclear, mainly coming from the lack of crystal structure of the Mac-1/GPIbα complex. We herein built a Mac-1/GPIbα complex model through a novel computer strategy, which included a flexible molecular docking and system equilibrium followed by a "force-ramp + snapback" molecular dynamics (MD) simulation. With this model, a series of "ramp-clamp" steered molecular dynamics (SMD) simulations were performed to examine the GPIbα-Mac-1 interaction under various loads. The results

SUBMITTER: Jiang X 

PROVIDER: S-EPMC8100526 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature