Molecular dynamics calculations of wild type vs. mutant protein C: Relationship between binding affinity to endothelial cell protein C receptor and hereditary disease

Molecular dynamics simulations of the protein C gamma-carboxyglutamic acid (Gla) domain and endothelial cell protein C receptor (EPCR) complex were performed to determine the effect of a hereditary disease, which results in a mutation (Gla 25 -> Lys) in the protein C Gla domain. Our results suggest that the Gla 25 -> Lys mutation causes a significant reduction in the binding force between protein C Gla domain and EPCR due to destabilization of the helix structure of EPCR and displacement of a Ca2+ ion.