Molecular Dynamics Study of IgM Antibody Complexes With Mutated SARS-CoV-2 Nucleocapsid Protein Antigen

Abstract

SARS-CoV-2 vaccine development remains challenging due to high viral mutation rates associated with spike protein targeting. This study explored nucleocapsid (N) protein as an alternative immunogenic antigen using in silico approaches. The N protein sequences from three SARS-CoV-2 variants endemic to Java Island (obtained from GISAID) and the Wuhan as the reference genome (NCBI) were subjected to molecular docking and molecular dynamics simulation. Protein-protein docking was performed by using ClusPro 2.0 with binding affinity analysis via PRODIGY. Molecular dynamics simulations (10 ns) were performed by using GROMACS 2026.1, with trajectory analysis involving root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bond occupancy, radius of gyration (Rg), and solvent-accessible surface area (SASA). The Wuhan variant showed the highest structural stability with optimal binding affinity of -12.8 kcal/mol. The East Java variant showed a good stability with binding affinity of -11.5 kcal/mol. The West Java variant showed a binding affinity value that was almost similar to the East Java variant, at -11.3 kcal/mol, but with more fluctuating structural stability. Meanwhile, the Central Java variant showed a good stability profile, but obtained the lowest binding affinity value of -7.6 kcal/mol which indicated the weakest binding affinity among the other variants.