Molecular dynamics simulation study of effects of key mutations in SARS-CoV-2 on protein structures

SARS-CoV-2 has been spreading rapidly since 2019 and has produced large-scale mutations in the genomes. Differences in gene sequences may lead to changes in protein structure and traits, which would have a great impact on the epidemiological characteristics. In this study, we selected the key mutations of SARS-CoV-2, including D614G and A222V of S protein and Q57H of ORF3a protein, to conduct molecular dynamics simulation and analysis on the structures of the mutant proteins. The results suggested that D614G improved the stability of S protein, while A222V enhanced the ability of protein to react with the outside environment. Q57H enhanced the structural flexibility of ORF3a protein. Our findings could complete the mechanistic link between genotype--phenotype--epidemiological characteristics in the study of SARS-CoV-2. We also found no significant changes in the antigenicity of S protein, ORF3a protein and their mutants, which provides reference for vaccine development and application.