Ricin is a highly lethal toxin.Anti-ricin chineric monoclonal antibody (mAb) C4Cl3 was prepared in our lab;however, its binding affinity was moch weaker than that of the parent antibody 4C13.In this study, based on the computer-guidcd homology modcling and confonmational optimization methods, the 3-D structurc of C4C13 variable rcgions Fv was construeted and optimized.Using molecular docking and dynamics simulation methods, the 3-D complcx structure of ricin and C4C13 Fv was obtained.Considering the orientation propcrty, surface electrostatic distribution, residues chemical andphysical charaeter and intermolccular hydrogcn bond, the binding mode and key residues were predicted.According to C4Cl3 Fv tragment and ricin complementary binding surface;electrostatic attractionpcriphery and van der Waals mteraction interface, three mutants (i.e., M I (N[1]02F, W[1]03Y);M2 (W[1]103Y) and M3 (R1.90G)) were designed, in which M1 and M2 were predicled to possess higher antigen-binding activity than C4Cl3, while M3 was weaker.The relative affinity assays by ELISA showed that M1 and M2 mutations had higher affinity (9.6 and 18.3nmol/L) than G4Cl3 (130nmol/L) and M3 had weaker affinity (234.5 nmol/L) than C4C l3.The results showed that the modeling complex structure of the antigen (ricin) and antibody (C4Cl3) is rea sonable.Our work offered affity maturated anlibodies by sile mutations, which were beneficial for valuable anti-ricin antibody design and preparation in future.