A simulation study on the adsorption orientation of DNA aptamer strands on MoS ₂ nanosheets

Adsorption of two anti-thrombin DNA aptamers (TBA-15 and TBA-29) onto a MoS ₂ nanosheet was investigated via six 200-ns all-atom molecular dynamics simulations in physiological salt solution, with different initial orientations and including scrambled and polyT control sequences. Regardless of starting configuration, all strands adopted a near-vertical orientation, contacting the MoS ₂ surface through a single terminal nucleotide. Van der Waals interactions dominated binding, contributing at least 88% of the binding energy, while electrostatic interactions were minor. Structural analyses (RMSD, RMSF, radius of gyration, hydrogen bonds) revealed that aptamer secondary structures remained largely intact upon adsorption, with restricted motion only at the anchored nucleotide. This vertical adsorption mode was consistent across strand lengths and sequences and was supported by umbrella sampling, which indicated a thermodynamic preference of 5–7 kcal mol ⁻¹ . These findings explain MoS ₂ -based aptasensor behavior and suggest attaching fluorescent labels opposite the anchoring nucleotide. This vertical adsorption mode was consistent across the two strand lengths and the four sequences examined in this study, and was supported by umbrella-sampling calculations performed for TBA-15 and TBA-29, which indicated a thermodynamic preference of 5–7 kcal mol ⁻¹ for the vertical adsorption mode along the center-of-mass distance coordinate; the orientational assignment of the free-energy minima was corroborated by the orientation-angle distributions resolved within the umbrella windows. Within the scope of the systems investigated, these findings provide a molecular-level rationale for the behavior of MoS ₂ -based aptasensors and suggest, subject to experimental validation, attaching fluorescent labels opposite the anchoring nucleotide.