# Deciphering Dickerson–Drew DNA Equilibrium beyond the BI/BII DNA Dichotomy by Interpretation of 31P NMR Parameters

## TL;DR

This paper improves the understanding of DNA structure by refining the interpretation of NMR data using a new classification and simulations.

## Contribution

A novel integration of NtC classification and MD simulations to interpret 31P NMR data in DNA.

## Key findings

- NtC classification and MD simulations reveal coexisting DNA backbone conformers.
- The approach improves the correspondence between NMR data and DNA structural heterogeneity.
- This method enhances the reliability of deducing DNA conformational equilibria in solution.

## Abstract

DNA duplexes exist
as dynamic ensembles of interconverting conformations
in solution. Conventional nuclear magnetic resonance (NMR) data interpretation
often simplifies this behavior by assuming one dominant structure,
but multiple substates (such as different backbone conformers) can
coexist. Here, we present an approach that refines the interpretation
of 31P NMR data in the Dickerson–Drew DNA by integrating
a nucleotide conformational classification (NtC) (Černý
et al., Nucleic Acids Research 2020, 48, 6367–6381) with molecular dynamics (MD) simulations. By
finely classifying backbone conformers into distinct NtC-defined states
and using MD to predict their populations, we achieve a more nuanced
correspondence between experimental NMR observables and DNA structure-dynamical
heterogeneity. Application of this framework demonstrates a radical
improvement of NMR data interpretation, thereby enhancing the reliability
of deducing DNA conformational equilibria in solution.