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Structural stability predictions and molecular dynamics simulations of RBD and HR1 mutations associated with SARS-CoV-2 spike glycoprotein.
J Biomol Struct Dyn. 2022 09; 40(15):6697-6709.JB

Abstract

The COVID-19 pandemic is caused by human transmission and infection of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). There is no trusted drug against the virus; hence, efforts are on discovering novel inhibitors for the virus. The entry of a SARS-CoV-2 virus particle into a host cell is initiated by its spike glycoprotein and host Angiotensin-Converting Enzyme 2 (ACE2) receptor interaction. Spike glycoprotein domains, namely, the Receptor Binding Domain (RBD) and Heptad Repeat (HR) domains, are essential for this activity. We have studied the impact of mutations such as A348T, N354D, D364Y, G476S, V483A, S494D in the RBD (319-591), and S939F, S940T, T941A, S943P (912-984) in the HR1 domains of spike glycoprotein. Summarily, we utilized the computational screening algorithms to rank the deleterious, damaging and disease-associated spike glycoprotein mutations. Subsequently, to understand the changes in conformation, flexibility and function of the spike glycoprotein mutants, Molecular Dynamics (MD) simulations were performed. The computational predictions and analysis of the MD trajectories suggest that the RBD and HR1 mutations induce significant phenotypic effects on the pre-binding spike glycoprotein structure, which are presumably consequential to its binding to the receptor and provides lead to design inhibitors against the binding.Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33618621

Citation

Ahamad, Shahzaib, et al. "Structural Stability Predictions and Molecular Dynamics Simulations of RBD and HR1 Mutations Associated With SARS-CoV-2 Spike Glycoprotein." Journal of Biomolecular Structure & Dynamics, vol. 40, no. 15, 2022, pp. 6697-6709.
Ahamad S, Hema K, Gupta D. Structural stability predictions and molecular dynamics simulations of RBD and HR1 mutations associated with SARS-CoV-2 spike glycoprotein. J Biomol Struct Dyn. 2022;40(15):6697-6709.
Ahamad, S., Hema, K., & Gupta, D. (2022). Structural stability predictions and molecular dynamics simulations of RBD and HR1 mutations associated with SARS-CoV-2 spike glycoprotein. Journal of Biomolecular Structure & Dynamics, 40(15), 6697-6709. https://doi.org/10.1080/07391102.2021.1889671
Ahamad S, Hema K, Gupta D. Structural Stability Predictions and Molecular Dynamics Simulations of RBD and HR1 Mutations Associated With SARS-CoV-2 Spike Glycoprotein. J Biomol Struct Dyn. 2022;40(15):6697-6709. PubMed PMID: 33618621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural stability predictions and molecular dynamics simulations of RBD and HR1 mutations associated with SARS-CoV-2 spike glycoprotein. AU - Ahamad,Shahzaib, AU - Hema,Kanipakam, AU - Gupta,Dinesh, Y1 - 2021/02/23/ PY - 2021/2/24/pubmed PY - 2022/8/30/medline PY - 2021/2/23/entrez KW - COVID-19 KW - RBD-HR1 mutations KW - SARS-CoV-2 KW - molecular dynamics simulations KW - spike glycoprotein SP - 6697 EP - 6709 JF - Journal of biomolecular structure & dynamics JO - J Biomol Struct Dyn VL - 40 IS - 15 N2 - The COVID-19 pandemic is caused by human transmission and infection of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). There is no trusted drug against the virus; hence, efforts are on discovering novel inhibitors for the virus. The entry of a SARS-CoV-2 virus particle into a host cell is initiated by its spike glycoprotein and host Angiotensin-Converting Enzyme 2 (ACE2) receptor interaction. Spike glycoprotein domains, namely, the Receptor Binding Domain (RBD) and Heptad Repeat (HR) domains, are essential for this activity. We have studied the impact of mutations such as A348T, N354D, D364Y, G476S, V483A, S494D in the RBD (319-591), and S939F, S940T, T941A, S943P (912-984) in the HR1 domains of spike glycoprotein. Summarily, we utilized the computational screening algorithms to rank the deleterious, damaging and disease-associated spike glycoprotein mutations. Subsequently, to understand the changes in conformation, flexibility and function of the spike glycoprotein mutants, Molecular Dynamics (MD) simulations were performed. The computational predictions and analysis of the MD trajectories suggest that the RBD and HR1 mutations induce significant phenotypic effects on the pre-binding spike glycoprotein structure, which are presumably consequential to its binding to the receptor and provides lead to design inhibitors against the binding.Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/33618621/Structural_stability_predictions_and_molecular_dynamics_simulations_of_RBD_and_HR1_mutations_associated_with_SARS_CoV_2_spike_glycoprotein_ L2 - https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1889671 DB - PRIME DP - Unbound Medicine ER -