Deep molecular modeling and mechanistic insights into type 2A von Willebrand disease with von Willebrand factor A2 domain mutations.

ABSTRACT:

Background

Type 2A von Willebrand disease (VWD) is characterized by impaired platelet adhesion due to the selective loss of high-molecular-weight von Willebrand factor (VWF) multimers.

Objectives

To investigate A2 domain variants underlying type 2A VWD and elucidate associated disease mechanisms through comprehensive VWF assays and structural modeling.

Methods

Sixty-five patients with 15 different VWF variants were investigated using full VWD phenotypic assays, underlying disease mechanisms, and genetic testing. Deep structural modeling (molecular dynamics, scaled molecular dynamics, and molecular docking) was employed to elucidate the effects of variants on the A2 domain.

Results

Laboratory findings confirmed impaired VWF function, with reduced VWF glyc

SUBMITTER: Seidizadeh O 

PROVIDER: S-EPMC12657285 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature