Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach.
ACE2 receptor
Binding affinity
Nonsynonymous mutations
SARS-CoV-2
Spike protein
Stability
Journal
Computers in biology and medicine
ISSN: 1879-0534
Titre abrégé: Comput Biol Med
Pays: United States
ID NLM: 1250250
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
28
01
2021
revised:
12
07
2021
accepted:
13
07
2021
pubmed:
5
8
2021
medline:
7
9
2021
entrez:
4
8
2021
Statut:
ppublish
Résumé
COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor. However, the molecular mechanism of pathological mutations of S-protein is still unclear. In this perspective, we investigated the impact of mutations in the S-protein and their interaction with the ACE2 receptor for SAR-CoV-2 viral infection. We examined the stability of pathological nonsynonymous mutations in the S-protein, and the binding behavior of the ACE2 receptor with the S-protein upon nonsynonymous mutations using the molecular docking and MM_GBSA approaches. Using the extensive bioinformatics pipeline, we screened the destabilizing (L8V, L8W, L18F, Y145H, M153T, F157S, G476S, L611F, A879S, C1247F, and C1254F) and stabilizing (H49Y, S50L, N501Y, D614G, A845V, and P1143L) nonsynonymous mutations in the S-protein. The docking and binding free energy (ddG) scores revealed that the stabilizing nonsynonymous mutations show increased interaction between the S-protein and the ACE2 receptor compared to native and destabilizing S-proteins and that they may have been responsible for the virulent high level. Further, the molecular dynamics simulation (MDS) approach reveals the structural transition of mutants (N501Y and D614G) S-protein. These insights might help researchers to understand the pathological mechanisms of the S-protein and provide clues regarding mutations in viral infection and disease propagation. Further, it helps researchers to develop an efficient treatment approach against this SARS-CoV-2 pandemic.
Identifiants
pubmed: 34346317
pii: S0010-4825(21)00448-0
doi: 10.1016/j.compbiomed.2021.104654
pmc: PMC8282961
pii:
doi:
Substances chimiques
Spike Glycoprotein, Coronavirus
0
Peptidyl-Dipeptidase A
EC 3.4.15.1
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104654Informations de copyright
Copyright © 2021. Published by Elsevier Ltd.
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