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    Rights statement: This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Biomolecular Structure and Dynamics on 21/12/2022, available online: https://www.tandfonline.com/doi/full/10.1080/07391102.2022.2158944

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Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells

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Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells. / Lin, Junqi; Anjum Huma, Farwa; Irfan, Aiza et al.
In: Journal of biomolecular structure & dynamics, Vol. 41, No. 20, 21.12.2023, p. 10762-10773.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Lin, J, Anjum Huma, F, Irfan, A, Ali, SS, Waheed, Y, Mohammad, A, Munir, M, Khan, A & Wei, D-Q 2023, 'Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells', Journal of biomolecular structure & dynamics, vol. 41, no. 20, pp. 10762-10773. https://doi.org/10.1080/07391102.2022.2158944

APA

Lin, J., Anjum Huma, F., Irfan, A., Ali, S. S., Waheed, Y., Mohammad, A., Munir, M., Khan, A., & Wei, D-Q. (2023). Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells. Journal of biomolecular structure & dynamics, 41(20), 10762-10773. https://doi.org/10.1080/07391102.2022.2158944

Vancouver

Lin J, Anjum Huma F, Irfan A, Ali SS, Waheed Y, Mohammad A et al. Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells. Journal of biomolecular structure & dynamics. 2023 Dec 21;41(20):10762-10773. Epub 2022 Dec 21. doi: 10.1080/07391102.2022.2158944

Author

Lin, Junqi ; Anjum Huma, Farwa ; Irfan, Aiza et al. / Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells. In: Journal of biomolecular structure & dynamics. 2023 ; Vol. 41, No. 20. pp. 10762-10773.

Bibtex

@article{474f9230b1154b3cbf0930c87992658c,
title = "Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells",
abstract = "The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants. ",
keywords = "Molecular Biology, General Medicine, Structural Biology",
author = "Junqi Lin and {Anjum Huma}, Farwa and Aiza Irfan and Ali, {Syed Shujait} and Yasir Waheed and Anwar Mohammad and Muhammad Munir and Abbas Khan and Dong-Qing Wei",
note = "This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Biomolecular Structure and Dynamics on 21/12/2022, available online: https://www.tandfonline.com/doi/full/10.1080/07391102.2022.2158944",
year = "2023",
month = dec,
day = "21",
doi = "10.1080/07391102.2022.2158944",
language = "English",
volume = "41",
pages = "10762--10773",
journal = "Journal of biomolecular structure & dynamics",
issn = "0739-1102",
publisher = "Taylor and Francis Ltd.",
number = "20",

}

RIS

TY - JOUR

T1 - Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells

AU - Lin, Junqi

AU - Anjum Huma, Farwa

AU - Irfan, Aiza

AU - Ali, Syed Shujait

AU - Waheed, Yasir

AU - Mohammad, Anwar

AU - Munir, Muhammad

AU - Khan, Abbas

AU - Wei, Dong-Qing

N1 - This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Biomolecular Structure and Dynamics on 21/12/2022, available online: https://www.tandfonline.com/doi/full/10.1080/07391102.2022.2158944

PY - 2023/12/21

Y1 - 2023/12/21

N2 - The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants.

AB - The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants.

KW - Molecular Biology

KW - General Medicine

KW - Structural Biology

U2 - 10.1080/07391102.2022.2158944

DO - 10.1080/07391102.2022.2158944

M3 - Journal article

VL - 41

SP - 10762

EP - 10773

JO - Journal of biomolecular structure & dynamics

JF - Journal of biomolecular structure & dynamics

SN - 0739-1102

IS - 20

ER -