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Direct detection of molecular intermediates from first-passage times.

Accepted version
Peer-reviewed

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Article

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Abstract

All natural phenomena are governed by energy landscapes. However, the direct measurement of this fundamental quantity remains challenging, particularly in complex systems involving intermediate states. Here, we uncover key details of the energy landscapes that underpin a range of experimental systems through quantitative analysis of first-passage time distributions. By combined study of colloidal dynamics in confinement, transport through a biological pore, and the folding kinetics of DNA hairpins, we demonstrate conclusively how a short-time, power-law regime of the first-passage time distribution reflects the number of intermediate states associated with each of these processes, despite their differing length scales, time scales, and interactions. We thereby establish a powerful method for investigating the underlying mechanisms of complex molecular processes.

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Keywords

31 Biological Sciences, 3102 Bioinformatics and Computational Biology, 51 Physical Sciences

Journal Title

Sci Adv

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

6

Publisher

American Association for the Advancement of Science (AAAS)

Rights

All rights reserved
Sponsorship
European Research Council (647144)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (674979)
A. L. T. and U. F. K. acknowledge funding from an ERC Consolidator Grant (DesignerPores 647144). J. G. was supported by an European Union Horizon 2020 research and innovation program under European Training Network (ETN) Grant No. 674979-NANOTRANS. H. B. acknowledges an ERC Advanced Grant (COSIMO 294443). Y. Q. acknowledges a China Scholarship Council-University of Oxford Scholarship. F. R. and M. R. acknowledge financial support from Grants Proseqo (FP7 EU program) FIS2016-80458-P (Spanish Research Council) and Icrea Academica prizes 2013 and 2018 (Catalan Government). A. B. K. acknowledges the support from the Welch Foundation (C-1559), from the NSF (CHE-1664218) and by the Center for Theoretical Biological Physics sponsored by the NSF (PHY-1427654).