Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations

Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective el...

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Main Authors: Walker-Gibbons, R, Zhu, X, Behjatian, A, Bennett, TJD, Krishnan, M
Format: Journal article
Language:English
Published: Nature Research 2024
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author Walker-Gibbons, R
Zhu, X
Behjatian, A
Bennett, TJD
Krishnan, M
author_facet Walker-Gibbons, R
Zhu, X
Behjatian, A
Bennett, TJD
Krishnan, M
author_sort Walker-Gibbons, R
collection OXFORD
description Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5–60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod—the simplest model of a nucleic acid—yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.
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spelling oxford-uuid:64067ef1-2f3e-4e4c-b7d4-355700923d1b2024-09-04T20:07:52ZSensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:64067ef1-2f3e-4e4c-b7d4-355700923d1bEnglishJisc Publications RouterNature Research2024Walker-Gibbons, RZhu, XBehjatian, ABennett, TJDKrishnan, MInferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5–60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod—the simplest model of a nucleic acid—yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.
spellingShingle Walker-Gibbons, R
Zhu, X
Behjatian, A
Bennett, TJD
Krishnan, M
Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title_full Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title_fullStr Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title_full_unstemmed Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title_short Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations
title_sort sensing the structural and conformational properties of single stranded nucleic acids using electrometry and molecular simulations
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