ArticleNucleic acids research2026
High-throughput measurement and prediction of the i-motif DNA stability landscape.
Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The i-motif, a cytosine-rich DNA secondary structure, exhibits pH- and temperature-dependent stability. We developed a high-throughput, five-dimensional ultraviolet melting/annealing (5DUVMA) method to systematically probe these dependencies. It enables the simultaneous assessment of thermal stability and pH sensitivity. Results show ionic strength and pH or temperature inversely affect thermal stability and pH sensitivity, respectively. A predictive mathematical model, powered by high-resolution 5DUVMA data, was established for bidirectional prediction of thermal stability and pH sensitivity. This framework was extended to decode multistep structural transitions in long C-tract i-motifs. We found that lower ionic strength and higher pH promote more melting steps and preferentially populate the less stable i-motif species. Our work provides a transformative platform and modeling approach for decoupling the complex environmental dependencies of nucleic acid structures.
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