Complementary to time-consuming wet lab study, computational methods are capable of providing a lot of details about protein-protein interaction binding pattern more than binding affinity. To our knowledge, no one has systematically studied the details of antibody-antigen binding and mutant effects for NTD yet using computing methods. Herein, we pay attention to in silico approaches to explore the crucial residues for NTD-antibody binding and predict mutational implications for neutralizing effectiveness. Methodically analyzing binding patterns by molecular dynamics (MD) simulation and end-point molecular mechanics generalized Born surface area (MM/GBSA) binding free energy calculation helps to shed light on the binding mechanisms of NTD-antibody. Our results revealed that mutations of some residues on NTD including Y144, K147, R246, Y248 have the high hazard of immune evasion for many antibodies and R246I mutation may reduce the efficacies of most current NTD antibodies through abolishing the hydrogen bond and electrostatic interaction with antibodies. Our research findings could be beneficial for drug design and mAbs-based therapeutics in clinical.