In silico screening and molecular dynamic simulation of RNA aptamers targeting Aurora A kinase (AURKA)

Significant progress has been made in developing cancer treatment; however, early cancer detection and management of chemotherapy-induced adverse effects remain major challenges. Aptamers, which are single-stranded DNA or RNA molecules, have gained considerable interest in biomedical applications due to their high affinity, stability, and less side effects. This study focused on analysing the interaction between Aurora A kinase (AUKRA) and specific RNA aptamers using in-silico method. The secondary (2D) and tertiary (3D) structure of aptamers were predicted using RNAFold web server, and RNAComposer, respectively. The aptamers were docked to the target protein using Auto-Dock 4.2.6 tool. Three aptamers, Seq1, Seq5 and Seq8, with best binding energy of -11.27, -10.91 and -9.22 Kcal/mol respectively, were selected. Through Molecular Dynamic (MD) simulation, we further confirmed the stability of the three aptamers-protein complexes. Simulation was done using NAMD 2.3 tool for 100 ns run time. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg) were used to evaluate structural variation. VMD were statistically analysed RMSD result. Interaction analysis was carried out using Protein Ligand Interaction Profiler (PLIP) and LigPlot. As a result Lys125, Tyr199, Arg189, Lys166, His54 etc. forms strong hydrogen bond between the AURKA and aptamer. Seq5 stands out the most structural stabile binding, while Seq8 targets the most crucial functional area of AURKA. Seq1, though stable, has a more limited binding interface and a somewhat lesser functional impact. Overall picture showed that Seq5 and Seq8 are the leading candidates for further biological validation and potential therapeutic development.