Molecular dynamics simulations of the SARS-CoV-2 Spike protein and variants of concern: structural evidence for convergent adaptive evolution.
Daniel Ferreira de Lima NetoVagner FonsecaRonaldo JesusLeonardo Hermes DutraLayssa Miranda de Oliveria PortelaCarla FreitasEduardo FillizolaBreno SoaresAndré Luiz de AbreuSandeep TwiariVasco Ariston de Carvalho AzevedoAristóteles Goes-NetoArnaldo Correia de MedeirosNorberto Peporine LopesPaolo Marinho de Andrade ZanottoRodrigo Bentes KatoPublished in: Journal of biomolecular structure & dynamics (2022)
The Spike protein's structure of the SARS-CoV-2 provides a unique opportunity to consider perturbations at the atomic level. We used the cryo-electron microscopy structure of the open conformation of the Spike protein to assess the impact of the mutations observed in the variants of concern at the molecular level. Molecular dynamics were subsequently performed with both the wt and the mutated forms to compare the flexibility and variation data for each residue of the three-dimensional fluctuations in the region associated with each alpha carbon. Additionally, protein-protein docking was used to investigate the interaction of each mutated profile with the ACE-2 receptor. After the molecular dynamics, the results show that the mutations increased the stability of the trimeric protein, with greater stability observed in the Gamma variant harboring the 10 characteristic mutations. The results of molecular dynamics, as shown by RMSF demonstrated for the residues that comprise the binding domain receptor (RBD), exhibited a reduction in flexibility, which was more pronounced in the Gamma variant. Finally, protein-protein docking experiments revealed an increase in the number of hydrophobic interactions and hydrogen bonds in the Gamma variant against the ACE-2 receptor, as opposed to the other variants. Taken together, these in silico experiments suggest that the evolution of the mutations favored the increased stability of Spike protein while potentially improving its interaction with the ACE-2 receptor, which in turn may indicate putative structural outcomes of the selection of these mutations in the convergent adaptive evolution as it has been observed for SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
Keyphrases
- molecular dynamics
- protein protein
- sars cov
- small molecule
- molecular dynamics simulations
- density functional theory
- binding protein
- electron microscopy
- copy number
- molecular docking
- amino acid
- angiotensin ii
- type diabetes
- high resolution
- gene expression
- single cell
- machine learning
- weight loss
- ionic liquid
- big data
- skeletal muscle
- dna binding
- transition metal