Edge Oxidation Redirects Coagulation Factor X Binding on Graphene Nanosheets: Insights from All-Atom Simulations

Graphene-based nanomaterials are increasingly used in biomedical applications, raising the likelihood of direct contact with coagulation factor X (FX), a key serine protease in blood coagulation. However, the molecular mechanisms underlying the interactions between FX and graphene-based nanomaterials remain poorly understood. In this study, we combined molecular docking with all-atom molecular dynamics simulations to elucidate the binding mechanisms of FX to graphene nanosheets with varying oxidation states. Our simulations reveal that pristine and epoxy-functionalized graphene preferentially interact with the catalytic (functional) domains of FX. In contrast, edge oxidation, especially with a higher density of carboxyl groups, shifts binding toward the Ca²⁺-coordinated γ-carboxyglutamic acid (Gla) domain, driven by enhanced electrostatic interactions. This edge-specific binding restricts the overall conformational flexibility of FX and induces rearrangement of key residues, potentially perturbing its catalytic activity. Moreover, the altered Gla-domain configuration may hinder membrane association, jointly leading to impaired coagulation function. Together, these findings identify edge carboxylation as a physical switch that modulates FX orientation and binding on graphene surfaces, providing molecular insights into the potential anticoagulant effects and informing the rational design of safer carbon-based nanomaterials.