We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol −1 ). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.
【저자키워드】 SARS-CoV-2, coronavirus, susceptibility, molecular dynamic simulation, pangolin, ACE2 variants, 【초록키워드】 ACE2, SARS-COV-2 infection, Human, Variation, virus transmission, binding free energy, database, binding affinity, Molecular dynamics simulation, human ACE2, SARS-CoV-2 spike protein, receptor, change, binding, Missense, significant increase, complex, wild-type, SNVs, significantly lower, Genes, dbSNP, greater, indicated, reduced, reduction in, single-nucleotide, 【제목키워드】 ACE2, variant, Infection, human ACE2, SARS-CoV-2 spike protein, binding, reveal,