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Background: Human complement receptor type 2 (CR2/CD21), a cell surface protein highly expressed on B cells and follicular dendritic cells, is a member of the regulators of complement activation protein family.C3d is a molecular adjuvant to diverse antigens and it is the primary ligand for CR2.The interactions between CR2 and C3d can bridge the innate and adaptive immune systems.Methods: The new crystal structure of CR2:C3d complex and three relevant three mutant systems (four systems are referred to as WT, R83A, D92A and K108A, respectively) were analyzed by molecular dynamics simulations.Functional dynamics and the conformational change of CR2 are exhibited by using domain cross-correlation map (DCCM), principal component analysis (PCA), and free energy landscape (FEL) methods.Results: The comparison of RMSD values shows that the structural stability of three mutants is decreased differently compared with WT, which is consistent with the experimental data.Based on the calculation of hydrogen bond at the interface, we analyze the loss of the stability of three mutants relative to WT.It is found that two clusters of residues (D36/ E37/E39 and E160/D163/E166) in the acidic pocket of C3d are important for CR2-C3d interactions, which is in good agreement with previous mutagenesis study.In addition, the conformational change corresponds to the opening of V-shaped structure of CR2, which is supported by high inter-domain flexibility of CR2 revealed by previous reports.Conclusions: We explain the loss of the binding stability of three mutants relative to WT and suppose that the opening of V-shaped structure of CR2 may favor the structural stability of CR2:C3d complex.This study can enhance the knowledge of the physicochemical properties on the CR2-C3d interactions at atomic level .