Thrombosis represents a major cause of morbidity and mortality around the world. Peptides isolated from natural sources have been proven to have anticoagulant and antithrombotic properties. VITPOR AI, a 16-mer peptide, isolated from Porphyra yezoensis was reported to have anticoagulant property. In this study, the coagulation factor XIIa activity in the presence of VITPOR AI was determined. Molecular modelling was performed to investigate the interaction between peptide and FXIIa. The structure of the peptide was predicted using PEP-FOLD3 server and simulated by molecular dynamics (MD) using GROMACS package. Molecular docking was carried out using peptide-protein docking software, pepATTRACT and its stability was confirmed by MD simulations. The chromogenic substrate assay revealed that the peptide inhibited the amidolytic activity of FXIIa with IC 50 of 70.24 μM. The docking result showed peptide interactions through hydrogen bonds with Pro 96, Tyr 99, Glu 146, Gly 193 and Ser 195 of FXIIa. The MD simulation demonstrated that the peptide's binding with the FXIIa was stable as it did not move away from its binding region throughout the simulation period of 100 ns Moreover, MM/PBSA analysis also indicated a stable binding between the protein and peptide. These results suggest that the inhibition of the FXIIa activity might be due to binding of the peptide to oxyanion hole of the catalytic site. Thus, VITPOR AI could be explored as a potent anticoagulant which inhibits only intrinsic pathway of coagulation cascade but does not affect the extrinsic pathway. © 2019 Elsevier Inc.