Molecular dynamics simulations reveal mechanistic insights into aptamer-induced structural rearrangements in viral capsid proteins

分子动力学模拟揭示了适体诱导病毒衣壳蛋白结构重排的机制。

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Abstract

Macrobrachium rosenbergii nodavirus is a major viral pathogen responsible for white tail disease in giant freshwater prawn aquaculture, leading to significant economic losses. In this study, a truncated DNA aptamer, TrAptm-1 was investigated for its binding properties against both monomeric and trimeric forms of the MrNV capsid proteins. Molecular dynamics simulations coupled with MM/PBSA binding free energy calculations revealed that TrAptm-1 exhibited a higher binding affinity to the trimeric capsid protein (-153.95 ± 6.74 kcal/mol) compared to the monomeric form (-120.77 ± 2.46 kcal/mol). TrAptm-1 binding induced significant conformational changes and structural rearrangements in the capsid protein, highlighted the antiviral potential of TrAptm-1 to interfere with the capsid protein self-assembly process. The observed structural changes demonstrated the importance of the oligomeric state in aptamer-capsid protein interactions, emphasizing that extended simulations up-to microseconds are required to capture the slow conformational rearrangements characteristic of large oligomeric protein complexes. These findings provide a molecular basis for the development of aptamer-based antiviral strategies, and the design of biosensor for early detection of MrNV in aquaculture settings.

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