Open AccessDistant residues modulate conformational opening in SARS-CoV-2 spike protein
Author(s) -
Dhiman Ray,
Ly Le,
Ioan Andricioaei
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100943118
Subject(s) - allosteric regulation , biology , coronavirus , protein structure , spike (software development) , mutation , spike protein , plasma protein binding , mutant , computational biology , receptor , drug discovery , genetics , covid-19 , bioinformatics , microbiology and biotechnology , gene , biochemistry , medicine , infectious disease (medical specialty) , economics , disease , management , pathology
Significance The novel coronavirus (SARS-CoV-2) pandemic resulted in the largest public health crisis in recent times. Significant drug design effort against SARS-CoV-2 is focused on the receptor-binding domain (RBD) of the spike protein, although this region is highly prone to mutations causing therapeutic resistance. We applied deep data analysis methods on all-atom molecular dynamics simulations to identify key non-RBD residues that play a crucial role in spike−receptor binding and infection. Because the non-RBD residues are typically conserved across multiple coronaviruses, they can be targeted by broad-spectrum antibodies and drugs to treat infections from new strains that might appear during future epidemics.