Molecular dynamics study of the temperature responsiveness of Cd²⁺ ion and its DNA aptamer: conformational memory and...

Cadmium ion (Cd²⁺) is a toxic environmental pollutant, and DNA aptamers are promising recognition elements for its detection. However, the dynamic response of aptamer-metal complexes to temperature cycling remains largely unexplored. Here, six independent all-atom molecular dynamics simulations (500 ns each) were performed to investigate a Cd²⁺-specific DNA aptamer under temperature cycling (300 K → 375 K → 300 K). A robust "conformational memory" effect was discovered. In the initial binding phase, Cd²⁺ coordinated exclusively with the O2 atom of residue DC12 (Cd-O ≈ 0.206 nm). Upon heating to 323-360 K, the ion fully dissociated. Notably, Cd²⁺ rebound at even higher temperatures (still during the heating ramp), but the coordination site irreversibly migrated to phosphate backbone oxygens (O1P/O2P) of different residues (Cd-O 0.200-0.202 nm). The average contacts per frame increased from 2.28 to 3.31. Dissociation and rebinding followed different free-energy branches, yielding clear temperature hysteresis loops (area 0.84-5.31 K·nm). Transition temperatures followed a normal distribution (mean 338.8 K, SD 10.3 K; Shapiro-Wilk p = 0.250), explained by a random-barrier model with activation energy fluctuations (E_a = 33.7 ± 1.0 kJ/mol). After thermal cycling, the DNA backbone became more flexible (RMSF increased from 0.207 nm to 0.422 nm), and the free-energy basin along the distance axis broadened from 0.19 nm to 0.39 nm, indicating a more expanded, entropically favored ensemble. These findings reveal an irreversible switch from nucleobase to backbone phosphate coordination, demonstrate conformational memory in a metal-aptamer system, and provide design principles for intelligent nucleic acid devices.