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单链核酸的纳秒级链动力学

Nanosecond chain dynamics of single-stranded nucleic acids.

作者信息

Nüesch Mark F, Pietrek Lisa, Holmstrom Erik D, Nettels Daniel, von Roten Valentin, Kronenberg-Tenga Rafael, Medalia Ohad, Hummer Gerhard, Schuler Benjamin

机构信息

Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438, Frankfurt am Main, Germany.

出版信息

Nat Commun. 2024 Jul 17;15(1):6010. doi: 10.1038/s41467-024-50092-8.

Abstract

The conformational dynamics of single-stranded nucleic acids are fundamental for nucleic acid folding and function. However, their elementary chain dynamics have been difficult to resolve experimentally. Here we employ a combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and nanophotonic enhancement to determine the conformational ensembles and rapid chain dynamics of short single-stranded nucleic acids in solution. To interpret the experimental results in terms of end-to-end distance dynamics, we utilize the hierarchical chain growth approach, simple polymer models, and refinement with Bayesian inference to generate structural ensembles that closely align with the experimental data. The resulting chain reconfiguration times are exceedingly rapid, in the 10-ns range. Solvent viscosity-dependent measurements indicate that these dynamics of single-stranded nucleic acids exhibit negligible internal friction and are thus dominated by solvent friction. Our results provide a detailed view of the conformational distributions and rapid dynamics of single-stranded nucleic acids.

摘要

单链核酸的构象动力学对于核酸折叠和功能至关重要。然而,其实质的链动力学一直难以通过实验解析。在此,我们结合单分子Förster共振能量转移、纳秒荧光相关光谱和纳米光子增强技术,以确定溶液中短单链核酸的构象集合和快速链动力学。为了根据端到端距离动力学来解释实验结果,我们利用分层链增长方法、简单聚合物模型以及贝叶斯推理进行优化,以生成与实验数据紧密匹配的结构集合。由此得到的链重构时间极快,在10纳秒范围内。溶剂粘度依赖性测量表明,这些单链核酸的动力学表现出可忽略不计的内摩擦,因此主要受溶剂摩擦主导。我们的结果提供了单链核酸构象分布和快速动力学的详细视图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/408a/11255343/68818f85d2ba/41467_2024_50092_Fig1_HTML.jpg

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