The Interaction of Factor Xa and IXa with Non-Activated Antithrombin in Michaelis Complex: Insights from Enhanced-Sampling Molecular Dynamics Simulations.

ABSTRACT: The interaction between coagulation factors Xa and IXa and the activated state of their inhibitor, antithrombin (AT),have been investigated using X-ray diffraction studies. However, only mutagenesis data are available for non-activated AT. Our aim was to propose a model based on docking and advanced-sampling molecular dynamics simulations that can reveal the conformational behavior of the systems when AT is not binding a pentasaccharide. We built the initial structure for non-activated AT-FXa and AT-FIXa complexes using HADDOCK 2.4. The conformational behavior was studied using Gaussian accelerated molecular dynamics simulations. In addition to the docked complexes, two systems based on the X-ray structures were also simulated, with and without the ligand. The simulations revealed large va

SUBMITTER: Balogh G 

PROVIDER: S-EPMC10216295 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature