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

Biological function is fundamentally determined by nucleic acid and protein sequence. Beyond encoding genetic information, nucleic acids also display complex physicochemical parameters that shape structure, dynamics, and interactions. Understanding how sequence variation sculpts the energetic landscapes underlying these properties requires methods that capture both molecular diversity and dynamic behavior. Single-molecule techniques are ideally suited to this task, but conventional formats remain time and cost intensive. Recent breakthroughs have enabled highly multiplexed approaches for observing molecular dynamics across millions of individual molecules representing thousands of sequences or barcoded entities. Though still in development, these methods have begun to bridge sequence, structure, dynamics, and function at scale, opening new opportunities in drug discovery, molecular diagnostics, and functional genomics.

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Publication Details

Journal
Science
Published
2026-01-29
DOI
https://doi.org/10.1126/science.adv4503
Citations
2
Primary Topic
Protein Degradation and Inhibitors
Type
article
Field-Weighted Citation Impact
44.47
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From sequence to function: Bridging single-molecule kinetics and molecular diversity

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article en
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Abstract

Biological function is fundamentally determined by nucleic acid and protein sequence. Beyond encoding genetic information, nucleic acids also display complex physicochemical parameters that shape structure, dynamics, and interactions. Understanding how sequence variation sculpts the energetic landscapes underlying these properties requires methods that capture both molecular diversity and dynamic behavior. Single-molecule techniques are ideally suited to this task, but conventional formats remain time and cost intensive. Recent breakthroughs have enabled highly multiplexed approaches for observing molecular dynamics across millions of individual molecules representing thousands of sequences or barcoded entities. Though still in development, these methods have begun to bridge sequence, structure, dynamics, and function at scale, opening new opportunities in drug discovery, molecular diagnostics, and functional genomics.

ScienceVol. 391(6784)
Uppsala University (SE), Ewha Womans University (KR), Science for Life Laboratory (SE), Huygens Institute for History and Culture of the Netherlands (NL), University of Oxford (GB), Delft University of Technology (NL)
Openalex Percentile: Top 0%
Protein Degradation and Inhibitors
44.47
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