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Journal article : Review

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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/science.adv4503

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Physics
Sub department:
Condensed Matter Physics
Oxford college:
St Cross College
Role:
Author
ORCID:
0000-0001-6699-136X
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Physics
Sub department:
Theoretical Physics
Role:
Author


More from this funder
Funder identifier:
10.13039/501100002794
Grant:
25 4453 P
More from this funder
Funder identifier:
10.13039/501100004359
Grant:
VR 03255
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Funder identifier:
https://ror.org/029chgv08
Grant:
110164/Z/15/Z
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Funder identifier:
https://ror.org/012mzw131
Grant:
RPG-2024-037
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Funder identifier:
https://ror.org/0472cxd90
Grant:
ERC-ADG-101092623


Publisher:
American Association for the Advancement of Science
Journal:
Science More from this journal
Volume:
391
Issue:
6784
Pages:
458-465
Publication date:
2026-01-29
Acceptance date:
2025-12-09
DOI:
EISSN:
1095-9203
ISSN:
0036-8075
Pmid:
41610253


Language:
English
Keywords:
Subtype:
Review
Pubs id:
2365868
Local pid:
pubs:2365868
Deposit date:
2026-02-23
ARK identifier:

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