SARS‐CoV‐2 spike evolutionary behaviors; simulation of N501Y mutation outcomes in terms of immunogenicity and structural characteristic

Rostami, Neda; Choupani, Edris; Hernandez, Yaeren; Arab, Seyed Shahriar; Jazayeri, Seyed Mohammad; Gomari, Mohammad Mahmoudi

doi:10.1002/jcb.30181

Cited by 10 publications

(6 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is a receptor binding motif (RBM) at positions 438 to 506 of the RBD region that directly interacts with ACE2 4 . Changes in the RBD play a significant role in immunity provocation and pathogenicity, for example, N501Y mutation enhances the affinity of the RBD for ACE2 and reduces the spike's immunogenicity 42 . To obtain an overview of the neutralization status of T and B cells for mutant compared to wild type, MCH‐I/II and linear/discontinuous epitopes were predicted (Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…4 Changes in the RBD play a significant role in immunity provocation and pathogenicity, for example, N501Y mutation enhances the affinity of the RBD for ACE2 and reduces the spike's immunogenicity. 42 To obtain an overview of the neutralization status of T and B cells for mutant compared to wild type, MCH-I/II and linear/discontinuous epitopes were predicted (Table 4). In terms of B cells, no difference was observed between mutant and wild types.…”

Section: Immunogenicity Analysismentioning

confidence: 99%

See 1 more Smart Citation

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Mondeali

Etemadi

Barkhordari

et al. 2023

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Immunogenicity Analysismentioning

confidence: 99%

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Mondeali

Etemadi

Barkhordari

et al. 2023

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The gyration radius (Rg) is the mass-weight root mean square distance of a group of atoms from their common center of mass 41 . Rg has been applied to better understand how complexes behave over time in molecular dynamics simulations and how this affects structural compactness 42 . Any ligand with a sufficiently high Rg value is more likely to be flexible, which makes it unstable.…”

Section: Resultsmentioning

confidence: 99%

In silico protein engineering shows that novel mutations affecting NAD+ binding sites may improve phosphite dehydrogenase stability and activity

Baammi

Daoud

Allali

2023

Sci Rep

View full text Add to dashboard Cite

Pseudomonas stutzeri phosphite dehydrogenase (PTDH) catalyzes the oxidation of phosphite to phosphate in the presence of NAD, resulting in the formation of NADH. The regeneration of NADH by PTDH is greater than any other enzyme due to the substantial change in the free energy of reaction (G°′ = − 63.3 kJ/mol). Presently, improving the stability of PTDH is for a great importance to ensure an economically viable reaction process to produce phosphite as a byproduct for agronomic applications. The binding site of NAD+ with PTDH includes thirty-four residues; eight of which have been previously mutated and characterized for their roles in catalysis. In the present study, the unexplored twenty-six key residues involved in the binding of NAD+ were subjected to in silico mutagenesis based on the physicochemical properties of the amino acids. The effects of these mutations on the structure, stability, activity, and interaction of PTDH with NAD+ were investigated using molecular docking, molecular dynamics simulations, free energy calculations, and secondary structure analysis. We identified seven novel mutations, A155I, G157I, L217I, P235A, V262I, I293A, and I293L, that reduce the compactness of the protein while improving PTDH stability and binding to NAD+.

show abstract

“…During the simulation, parameters such as the root mean square deviation (RMSD), 52 root mean square fluctuation (RMSF), 53 the radius of gyration (RG), 54 solvent‐accessible surface area (SASA), 55 free energy landscape (FEL), 56 and principal component analysis (PCA), 57 were employed for checking structure attributes of complexes. In addition, the number of H‐bonds, 58 minimum distance, 59 and the number of contacts 60 were examined for analysis of CD44 interaction with designed peptides. MD simulation was accomplished by the GROMACS ( v2021.2 ) software package 61 .…”

Section: Methodsmentioning

confidence: 99%

Rational peptide design for targeting cancer cell invasion

Gomari,

Arab,

Balalaie

et al. 2023

Proteins

View full text Add to dashboard Cite

Cell invasion is an important process in cancer progression and recurrence. Invasion and implantation of cancer cells from their original place to other tissues, by disabling vital organs, challenges the treatment of cancer patients. Given the importance of the matter, many molecular treatments have been developed to inhibit cancer cell invasion. Because of their low production cost and ease of production, peptides are valuable therapeutic molecules for inhibiting cancer cell invasion. In recent years, advances in the field of computational biology have facilitated the design of anti‐cancer peptides. In our investigation, using computational biology approaches such as evolutionary analysis, residue scanning, protein–peptide interaction analysis, molecular dynamics, and free energy analysis, our team designed a peptide library with about 100 000 candidates based on A6 (acetyl‐KPSSPPEE‐amino) sequence which is an anti‐invasion peptide. During computational studies, two of the designed peptides that give the highest scores and showed the greatest sequence similarity to A6 were entered into the experimental analysis workflow for further analysis. In experimental analysis steps, the anti‐metastatic potency and other therapeutic effects of designed peptides were evaluated using MTT assay, RT‐qPCR, zymography analysis, and invasion assay. Our study disclosed that the IK1 (acetyl‐RPSFPPEE‐amino) peptide, like A6, has great potency to inhibit the invasion of cancer cells.

show abstract

SARS‐CoV‐2 spike evolutionary behaviors; simulation of N501Y mutation outcomes in terms of immunogenicity and structural characteristic

Cited by 10 publications

References 53 publications

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

In silico protein engineering shows that novel mutations affecting NAD+ binding sites may improve phosphite dehydrogenase stability and activity

Rational peptide design for targeting cancer cell invasion

Contact Info

Product

Resources

About