Chemical probing experiments such as SHAPE are routinely used to probe RNA molecules. In this work, we use atomistic molecular dynamics simulations to test the hypothesis that binding of RNA with SHAPE reagents is affected by cooperative effects leading to an observed reactivity that is dependent on the reagent concentration. We develop a general technique that enables the calculation of the affinity for arbitrary molecules as a function of their concentration in the grand-canonical ensemble. Our simulations of an RNA structural motif suggest that, at the concentration typically used in SHAPE experiments, cooperative binding would lead to a measurable concentration-dependent reactivity. We also provide a qualitative validation of this statement by analyzing a new set of experiments collected at different reagent concentrations.

Molecular Dynamics Simulations with Grand-Canonical Reweighting Suggest Cooperativity Effects in RNA Structure Probing Experiments / Calonaci, Nicola; Bernetti, Mattia; Jones, Alisha; Sattler, Michael; Bussi, Giovanni. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - 19:12(2023), pp. 3672-3685. [10.1021/acs.jctc.3c00084]

Molecular Dynamics Simulations with Grand-Canonical Reweighting Suggest Cooperativity Effects in RNA Structure Probing Experiments

Calonaci, Nicola;Bernetti, Mattia;Bussi, Giovanni
2023-01-01

Abstract

Chemical probing experiments such as SHAPE are routinely used to probe RNA molecules. In this work, we use atomistic molecular dynamics simulations to test the hypothesis that binding of RNA with SHAPE reagents is affected by cooperative effects leading to an observed reactivity that is dependent on the reagent concentration. We develop a general technique that enables the calculation of the affinity for arbitrary molecules as a function of their concentration in the grand-canonical ensemble. Our simulations of an RNA structural motif suggest that, at the concentration typically used in SHAPE experiments, cooperative binding would lead to a measurable concentration-dependent reactivity. We also provide a qualitative validation of this statement by analyzing a new set of experiments collected at different reagent concentrations.
2023
19
12
3672
3685
10.1021/acs.jctc.3c00084
https://arxiv.org/abs/2209.12640
Calonaci, Nicola; Bernetti, Mattia; Jones, Alisha; Sattler, Michael; Bussi, Giovanni
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/132690
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