From sequence to function
Bridging single-molecule kinetics and molecular diversity
A. N. Kapanidis (University of Oxford)
L. Muras (Uppsala University)
K. Sreenivasa (Kavli institute of nanoscience Delft, TU Delft - Applied Sciences)
J. P. Hazra (University of Oxford)
J. van Noort (Universiteit Leiden)
C. Joo (TU Delft - Applied Sciences, TU Delft - Applied Sciences, Ewha Woman’s University)
S. Deindl (Uppsala University)
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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.