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

• 成果类型: Review
• 署名作者: Kapanidis, A. N.; Muras, L.; Sreenivasa, K.; Hazra, J. P.; van Noort, J.; Joo, C.; Deindl, S.
• 署名单位: University of Oxford; University of Oxford; Uppsala University; Delft University of Technology; Leiden University; Leiden University - Excl LUMC; Ewha Womans University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adv4503
• 发表日期: 2026-01-29
• 关键词: rna-protein interactions; IN-VITRO SELECTION; high-throughput; energy-transfer; dna; transcription; polymerase; generation; DYNAMICS; reveals

摘要

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.