Key residues regulating von Willebrand factor A1/A2 interactions: insights from molecular dynamics simulations and experimental validation.

ABSTRACT:

Background

Von Willebrand factor (VWF), secreted by endothelial cells and megakaryocytes, plays a critical role in hemostasis. Under normal physiological conditions, VWF adopts a globular conformation in which the glycoprotein Ibα-binding site on A1 domain is occluded by the adjacent A2 domain. Studies indicate that exogenous free A2 fragments can improve coagulation function following traumatic brain injury by competitively binding to endogenous VWF-A1, highlighting the therapeutic potential of targeting A1/A2 interaction.

Objectives

This study aimed to identify key residues regulating the A1/A2 interaction at the interface.

Methods

In this study, we used the HADDOCK platform to obtain the optimal conformation of A1/A2 complex and used molecular dynamics simulations

SUBMITTER: Fang J 

PROVIDER: S-EPMC12743552 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature