In the face of the severe epidemic of COVID-19, it is urgent to have a deep understanding of molecular mechanisms of harmful mutations and the vital antigenic epitopes when we are developing treatment and prevention methods. This paper applied a series of in silico methods to explore the binding patterns of different antibodies to S protein NTD. By per residue energy decomposition, some residues, including R246, Y144, K147 and Y248, are found to play a crucial role in multiple NTD-specific antibodies binding. This result reminds us that mutations of these residues has the potential to cause immune evasion. By the means of MD simulation and MM/GBSA calculation, we predicted that R246I mutation may decrease or even invalidate the effectiveness of some mAbs. Further analysis of the molecular mechanism revealed that the immune escape of R246I mutation from 5-24 could be, to a great degree, attributed to the abolishment of the strong hydrogen bonds and electrostatic attractions between R246 of NTD and D105 of antibody. The findings in this study makes it possible to optimize existing therapeutic antibodies, thus making them more efficacious against COVID-19.