In silico conversion of ssRNA aptamers to ssDNA: molecular dynamics assessment of structural stability and conformational preservation

Abstract

The application of single-stranded RNA (ssRNA) aptamers may be limited by their chemical instability and susceptibility to enzymatic degradation, despite their high structural specificity. Thus, this study presents a computational workflow for the rational conversion of ssRNA aptamers (A6 and A11), previously selected for prostate cancer cells, into structurally preserved single-stranded DNA (ssDNA) analogues, termed LN-A6 and LN-A11. The workflow integrates three-dimensional structural modeling, targeted chemical modifications, and molecular dynamics simulations conducted for 200 ns at 300 K and 310 K, aiming to assess conformational preservation under different thermal conditions. Structural comparisons between ssRNA and ssDNA were performed using widely adopted molecular dynamics descriptors, including root-mean-square deviation and the number of intramolecular hydrogen bonds throughout the simulation trajectories. The results indicate that the ssDNA variants retained key structural features of their ssRNA precursors, exhibiting consistent conformational behavior at both analyzed temperatures. Although the ssRNA aptamers displayed more conformationally restricted architectures, the ssDNA analogues preserved sufficient structural integrity to support the feasibility of the conversion from a conformational standpoint. Overall, this study describes a reproducible computational workflow for evaluating structural preservation during the conversion of ssRNA to ssDNA aptamers, providing a methodological foundation for future experimental investigations.