Chen Fei LowNorazli GhadinMuhamad Arif Mohamad Jamali2025-07-292025-07-2920252025-7-28Low, C. F., Norazli Ghadin&Muhamad Arif Mohamad Jamali2. (2025). Molecular dynamics simulations reveal mechanistic insights into aptamer-induced structural rearrangements in viral capsid proteins. Journal of Computer-Aided Molecular Design, 39(1). https://doi.org/10.1007/s10822-025-00633-00920-654X2538-7https://doi.org/10.1007/s10822-025-00633-0https://oarep.usim.edu.my/handle/123456789/27312https://link.springer.com/article/10.1007/s10822-025-00633-0Indexed by WOS/Scopus/ERAMacrobrachium 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.en-USAptamerViral capsid proteinConformational changesBinding affinitytext::journal::journal article1123957