Mechanisms of ssDNA aptamer binding to Cd²⁺ in aqueous solution: A molecular dynamics study

ssDNA aptamers have been increasingly used to detect heavy metal ions as recognition elements due to their high affinity and specificity. However, the specific recognition and binding mechanisms between aptamers and most heavy metals were still unclear, which limits the development of aptamer-based detection methods. In this work, the interaction mechanisms of CD-2-1 aptamers with Cd²⁺ in aqueous solutions were investigated using molecular dynamic simulations. The most stable complex was found where Cd²⁺ binding at aptamer's stem-loop junction and preferred at the phosphate backbone or bases. Noteworthily, two binding modes of Cd²⁺ combining aptamer in aqueous solution were discovered: direct and indirect. In the former mode, Cd²⁺ directly coordinated O atoms of bases. For the latter, Cd²⁺ connected to bases with coordinated water molecules as bridges. Electrostatic interaction was found to be the main driving force, and differences of residues role between two binding modes were elucidated. Buffer molecules in aqueous solutions can stabilize aptamer-Cd²⁺ complex by hydrogen bonds. This study revealed the specific interaction mechanisms of aptamer with Cd²⁺ at an atomic level, which provided theoretical references for aptamer-based Cd²⁺ detection methods establishment as well as an efficient technical route of screening potential aptamers for heavy metal ions.