Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain

Pitsillou, Eleni; Liang, Julia; Beh, Raymond C.; Hung, Andrew; Karagiannis, Tom C.

doi:10.1016/j.compbiomed.2022.106035

Cited by 16 publications

(12 citation statements)

References 88 publications

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“…Although the QSAR modelling mainly relies on the original experimental data, we can further investigate the potential inhibitors by combining chemometrics, which is a combination of QSAR modelling, molecular docking and MD simulation. Molecular docking and MD simulation can directly target compounds to the protein crystals of variants, analyse the binding affinity and stability of compounds to different variant proteins, and directly assess whether the compounds can interact with the new variants [ 112 , 113 ].…”

Section: Opportunities and Challenges Of Computational Modelling Methodsmentioning

confidence: 99%

Recent advances in chemometric modelling of inhibitors against SARS-CoV-2

Wang,

Lu,

Jia

et al. 2024

Heliyon

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Section: Opportunities and Challenges Of Computational Modelling Methodsmentioning

confidence: 99%

Recent advances in chemometric modelling of inhibitors against SARS-CoV-2

Wang,

Lu,

Jia

et al. 2024

Heliyon

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“…269,276 A simulation study using the pyDockEneRes tool 277 showed that the mutations L452R and T478K in the Delta variant increase the strength of ACE2 binding. 278…”

Section: Delta Variantmentioning

confidence: 99%

“…Pitsillou et al 278 showed that Omicron BA.1 displays higher binding affinity for ACE2 than Delta and WT when using pyDockEneRes with CHARM36 force field and TIP3P water. The fragment molecular orbital method revealed mutations S371L, S375F, N440K, T478K, E484A, Q493K, and Q498R significantly enhance interaction with ACE2.…”

Section: Omicron Variantmentioning

confidence: 99%

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

Nguyen,

Lan

et al. 2023

Chem. Soc. Rev.

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“…There has been an intensive effort aimed at understanding the spike–cell receptor and spike–antibody interactions using computational chemistry and especially molecular mechanics/molecular dynamics (MM/MD) tools [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. The study of protein associations by MM/MD calculations represents a grand challenge in computational biochemistry since they involve the study of protein–protein interactions (PPIs), a difficult task given the size of the systems involved and the fact that protein–protein interactions (like antibody–antigen) are mediated by residue residents in loops, the most flexible secondary structure [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Diverse Nature of the Molecular Interactions That Govern the COV-2 Variants’ Cell Receptor Affinity Ranking and Its Experimental Variability

Sussman,

Villaverde

2024

IJMS

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A critical determinant of infectivity and virulence of the most infectious and or lethal variants of concern (VOCs): Wild Type, Delta and Omicron is related to the binding interactions between the receptor-binding domain of the spike and its host receptor, the initial step in cell infection. It is of the utmost importance to understand how mutations of a viral strain, especially those that are in the viral spike, affect the resulting infectivity of the emerging VOC, knowledge that could help us understand the variant virulence and inform the therapies applied or the vaccines developed. For this sake, we have applied a battery of computational protocols of increasing complexity to the calculation of the spike binding affinity for three variants of concern to the ACE2 cell receptor. The results clearly illustrate that the attachment of the spikes of the Delta and Omicron variants to the receptor originates through different molecular interaction mechanisms. All our protocols unanimously predict that the Delta variant has the highest receptor-binding affinity, while the Omicron variant displays a substantial variability in the binding affinity of the spike that relates to the structural plasticity of the Omicron spike–receptor complex. We suggest that the latter result could explain (at least in part) the variability of the in vitro binding results for this VOC and has led us to suggest a reason for the lower virulence of the Omicron variant as compared to earlier strains. Several hypotheses have been developed around this subject.

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Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain

Cited by 16 publications

References 88 publications

Recent advances in chemometric modelling of inhibitors against SARS-CoV-2

Recent advances in chemometric modelling of inhibitors against SARS-CoV-2

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

The Diverse Nature of the Molecular Interactions That Govern the COV-2 Variants’ Cell Receptor Affinity Ranking and Its Experimental Variability

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