Design and characterization of modified RNA G-quadruplex for Tl⁺ ion leaching: Insights from computer simulations

Metal ions are essential to numerous biological functions, yet their accumulation in the environment can lead to serious health and ecological concerns. Thallium ions, in particular, are highly toxic and frequently enter aquatic ecosystems through industrial discharge, where they can bioaccumulate in organisms and pose risks to human health. Conventional detection and removal methods, such as mass spectrometry, ion exchange, and chemical precipitation, often suffer from low specificity, high cost, and operational complexity. Nucleic acid-based nanostructures, especially RNA G-quadruplexes, offer a promising alternative due to their precise ion-binding ability and structural flexibility. In this study, we designed a chemically modified RNA G-quadruplex with the aim of improving both its binding specificity for thallium ions and its structural resilience. Using all-atom explicit-solvent molecular dynamics simulations (400 ns, 3 replicas each), we examined the behaviour of this modified structure in the presence of potassium, cesium, and thallium ions. The modified quadruplex demonstrated enhanced selectivity and stable binding with thallium ions within the central guanine tetrad, showing superior performance compared to the unmodified version. The chemical modifications are also expected to increase resistance to enzymatic degradation, further supporting their utility in practical applications. These findings highlight the potential of engineered RNA G-quadruplexes as molecular platforms for the selective recognition and sequestration of toxic metal ions such as thallium. This work lays the foundation for developing modified RNA-based biosensors and bioremediation tools for environmental monitoring and public health protection.