The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective. Issue 2 (7th January 2023)

• Record Type: Journal Article
• Authors: Mondeali, Mozhgan; Etemadi, Ali; Barkhordari, Khabat; Mobini Kesheh, Mina; Shavandi, Sara; Bahavar, Atefeh; Tabatabaie, Fatemeh Hosseini; Mahmoudi Gomari, Mohammad; Modarressi, Mohammad H.
• Is Part Of: Journal of cellular biochemistry. Volume 124:Issue 2(2023)
• Page Start: 308
• Page End: 319
• Publication Date: 2023-01-07
• Subjects: molecular docking -- molecular dynamics (MD) simulation -- molecular interactionss -- SARS‐CoV‐2 -- S477N mutation; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.30367
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: The attachment of SARA‐CoV‐2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD. Today's computational approaches in biology, especially during the SARS‐CoV‐2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N‐hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein–protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD‐ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC‐II.