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Computational Insights on the Assembly of the Dengue Virus Membrane-Capsid-RNA Complex.

Dwaipayan Chaudhuri·Satyabrata Majumder·Joyeeta Datta·Kalyan Giri
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Abstract

Dengue virus, an arbovirus from the genus Flavivirus in the family Flaviviridae, forms a nucleocapsid structure through interactions between its genome and multiple copies of the capsid protein. Experimental studies have confirmed the interaction between the viral capsid protein and lipid droplets, indicating a protein-lipid interaction. Cryo-EM studies show that in immature viruses, the nucleocapsid is located close to the viral membrane. This study uses multiple MD simulations to explore the orientation of the capsid protein relative to the lipid membrane, focusing on how the protein's hydrophobic pocket interacts with the membrane. We also investigated the interaction between the capsid protein and RNA, considering the effects of sequence length and identity. Finally, we construct a model of the lipid-protein-RNA complex, demonstrating that the capsid protein's hydrophobic pocket interacts with the membrane, while the positively charged H4 helix interacts with the negatively charged RNA. This research may identify crucial interactions for immature virus particle formation and provide insights for future therapeutic interventions.

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Dengue VirusRNA, ViralCapsid ProteinsMolecular Dynamics SimulationVirus AssemblyCapsidHydrophobic and Hydrophilic InteractionsProtein BindingCapsid–RNA interactionCapsid–lipid interactionDengue virusMD simulationNucleocapsidJournal Article

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Dwaipayan Chaudhuri, Satyabrata Majumder, Joyeeta Datta, Kalyan Giri. 2025-01-19. Computational Insights on the Assembly of the Dengue Virus Membrane-Capsid-RNA Complex.. https://doi.org/10.1007/s00232-025-00337-4

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