tetano
Editor, Senior Moderator
Protein J
. 2022 Aug 1.
doi: 10.1007/s10930-022-10065-6. Online ahead of print.
Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations
Alec J Wozney[SUP] 1 [/SUP], Macey A Smith[SUP] 1 [/SUP], Mobeen Abdrabbo[SUP] 1 [/SUP], Cole M Birch[SUP] 1 [/SUP], Kelsey A Cicigoi[SUP] 1 [/SUP], Connor C Dolan[SUP] 1 [/SUP], Audrey E L Gerzema[SUP] 1 [/SUP], Abby Hansen[SUP] 1 [/SUP], Ethan J Henseler[SUP] 1 [/SUP], Ben LaBerge[SUP] 1 [/SUP], Caterra M Leavens[SUP] 1 [/SUP], Christine N Le[SUP] 1 [/SUP], Allison C Lindquist[SUP] 1 [/SUP], Rikaela K Ludwig[SUP] 1 [/SUP], Maggie G O'Reilly[SUP] 1 [/SUP], Jacob H Reynolds[SUP] 1 [/SUP], Brandon A Sherman[SUP] 1 [/SUP], Hunter W Sillman[SUP] 1 [/SUP], Michael A Smith[SUP] 1 [/SUP], Marissa J Snortheim[SUP] 1 [/SUP], Levi M Svaren[SUP] 1 [/SUP], Emily C Vanderpas[SUP] 1 [/SUP], Aidan Voon[SUP] 1 [/SUP], Miles J Wackett[SUP] 1 [/SUP], Moriah M Weiss[SUP] 1 [/SUP], Sanchita Hati[SUP] 2 [/SUP], Sudeep Bhattacharyya[SUP] 3 [/SUP]
Affiliations
Abstract
Using molecular dynamics simulations, the protein-protein interactions of the receptor-binding domain of the wild-type and seven variants of the severe acute respiratory syndrome coronavirus 2 spike protein and the peptidase domain of human angiotensin-converting enzyme 2 were investigated. These variants are alpha, beta, gamma, delta, eta, kappa, and omicron. Using 100 ns simulation data, the residue interaction networks at the protein-protein interface were identified. Also, the impact of mutations on essential protein dynamics, backbone flexibility, and interaction energy of the simulated protein-protein complexes were studied. The protein-protein interface for the wild-type, delta, and omicron variants contained several stronger interactions, while the alpha, beta, gamma, eta, and kappa variants exhibited an opposite scenario as evident from the analysis of the inter-residue interaction distances and pair-wise interaction energies. The study reveals that two distinct residue networks at the central and right contact regions forge stronger binding affinity between the protein partners. The study provides a molecular-level insight into how enhanced transmissibility and infectivity by delta and omicron variants are most likely tied to a handful of interacting residues at the binding interface, which could potentially be utilized for future antibody constructs and structure-based antiviral drug design.
Keywords: COVID-19; Delta; Molecular dynamics; Omicron; SARS-CoV-2; Spike protein.
. 2022 Aug 1.
doi: 10.1007/s10930-022-10065-6. Online ahead of print.
Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations
Alec J Wozney[SUP] 1 [/SUP], Macey A Smith[SUP] 1 [/SUP], Mobeen Abdrabbo[SUP] 1 [/SUP], Cole M Birch[SUP] 1 [/SUP], Kelsey A Cicigoi[SUP] 1 [/SUP], Connor C Dolan[SUP] 1 [/SUP], Audrey E L Gerzema[SUP] 1 [/SUP], Abby Hansen[SUP] 1 [/SUP], Ethan J Henseler[SUP] 1 [/SUP], Ben LaBerge[SUP] 1 [/SUP], Caterra M Leavens[SUP] 1 [/SUP], Christine N Le[SUP] 1 [/SUP], Allison C Lindquist[SUP] 1 [/SUP], Rikaela K Ludwig[SUP] 1 [/SUP], Maggie G O'Reilly[SUP] 1 [/SUP], Jacob H Reynolds[SUP] 1 [/SUP], Brandon A Sherman[SUP] 1 [/SUP], Hunter W Sillman[SUP] 1 [/SUP], Michael A Smith[SUP] 1 [/SUP], Marissa J Snortheim[SUP] 1 [/SUP], Levi M Svaren[SUP] 1 [/SUP], Emily C Vanderpas[SUP] 1 [/SUP], Aidan Voon[SUP] 1 [/SUP], Miles J Wackett[SUP] 1 [/SUP], Moriah M Weiss[SUP] 1 [/SUP], Sanchita Hati[SUP] 2 [/SUP], Sudeep Bhattacharyya[SUP] 3 [/SUP]
Affiliations
- PMID: 35913554
- DOI: 10.1007/s10930-022-10065-6
Abstract
Using molecular dynamics simulations, the protein-protein interactions of the receptor-binding domain of the wild-type and seven variants of the severe acute respiratory syndrome coronavirus 2 spike protein and the peptidase domain of human angiotensin-converting enzyme 2 were investigated. These variants are alpha, beta, gamma, delta, eta, kappa, and omicron. Using 100 ns simulation data, the residue interaction networks at the protein-protein interface were identified. Also, the impact of mutations on essential protein dynamics, backbone flexibility, and interaction energy of the simulated protein-protein complexes were studied. The protein-protein interface for the wild-type, delta, and omicron variants contained several stronger interactions, while the alpha, beta, gamma, eta, and kappa variants exhibited an opposite scenario as evident from the analysis of the inter-residue interaction distances and pair-wise interaction energies. The study reveals that two distinct residue networks at the central and right contact regions forge stronger binding affinity between the protein partners. The study provides a molecular-level insight into how enhanced transmissibility and infectivity by delta and omicron variants are most likely tied to a handful of interacting residues at the binding interface, which could potentially be utilized for future antibody constructs and structure-based antiviral drug design.
Keywords: COVID-19; Delta; Molecular dynamics; Omicron; SARS-CoV-2; Spike protein.