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

Science, vol. 391, pp. 458–465

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.

Authors 7

1. Achillefs N. Kapanidis corresponding

   University of Oxford

   Affiliation as printed

   Department of Physics, University of Oxford, Oxford, UK

   Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK

2. L. Muras

   Uppsala University · Science for Life Laboratory

   Affiliation as printed

   Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

3. Koushik Sreenivasa

   Delft University of Technology

   Affiliation as printed

   Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands

4. Jagadish Prasad Hazra

   University of Oxford

   Affiliation as printed

   Department of Physics, University of Oxford, Oxford, UK

   Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK

5. John van Noort Aachen Biological and Soft Matter Physics Huygens-Kamerlingh Onnes Laboratory

   Leiden University

   Affiliation as printed

   Biological and Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, Netherlands

6. Chirlmin Joo

   Ewha Womans University · Delft University of Technology

   Affiliation as printed

   Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands

   Department of Physics, Ewha Womans University, Seoul, Republic of Korea

7. Sebastian Deindl corresponding

   Uppsala University · Science for Life Laboratory

   Affiliation as printed

   Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden