Analysis of P12 Binding Behavior at the N-Terminal of αC Domain and Central E Domain of Fibrinogen Structure

While blood clotting is essential for preventing blood loss, abnormal fibrin formation on surfaces can cause serious conditions such as thrombosis or stroke. P12, a 14-residue peptide derived from fibronectin, has shown potential in modulating fibrin assembly, but its molecular targets remain unclear. In vivo studies indicate that the N-terminal of the αC domain and the central E domain of fibrinogen are key determinants of P12 dynamics. Thus, we conducted an in silico analysis of P12 as a potential inhibitor of these domains through molecular dynamics (MD) simulations and protein-peptide docking. We aim to clarify P12’s binding preference and role in fibrin formation, contributing to the development of safer antithrombotic medicines.

P12 conformers were generated through MD and docked to each domain using ClusPro; top poses were refined in 100 ns MD production runs, followed by binding free energy analysis using gmx_MMPBSA.

Our results found that P12 binds both domains, but exhibits a stronger interaction with the αC N-terminal (−63.8 ± 7.2 kcal/mol) compared to the E domain (−24.9 ± 4.6 kcal/mol). Structural metrics supported this: the αC complex showed lower SASA and more residue contacts. These findings suggest that P12 preferentially targets αC and may influence fibrin formation through this interaction. Future work will investigate αC as a potential therapeutic target for drugs to prevent excessive clotting safely.