From sequence to function: Bridging single-molecule kinetics and molecular diversity

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.adv4503?af=R...

Published: 2026-01-29T07:00:02Z

Scientists have developed the SPARXS (Single-molecule Parallel Analysis for Rapid eXploration of Sequence space) method, which combines single-molecule fluorescence with next-generation sequencing.[1][2] This technique enables high-throughput molecular dynamics studies and overcomes the problem of laborious assays for large sequence libraries.[1][2] They applied it to the kinetics of the Holliday junction, a key intermediate in homologous recombination.[1][2] They analyzed the dynamics of millions of Holliday junctions covering thousands of different sequences.[1][2] SPARXS revealed sequence patterns, evaluated sequence motifs, and allowed thermodynamic models to be constructed.[1][2] The method makes it possible to examine millions of DNA molecules at once, which speeds up screening thousands of times compared to previous procedures.[4] The study was published in the journal Science in 2024.[1][2]