Backbone equilibrium in mismatched DNA influenced by solution conditions

Abstract

The impact of solution conditions on the 31P isotropic chemical shifts of DNA phosphates and therefore the sequence-dependent backbone conformational equilibrium has not been well-documented. There are no previous studies of DNA backbone equilibrium in the presence of crowding agents, nor any on mismatched DNA. A systematic study of several experimental conditions (Na+ concentration, K+ concentration, Mg2+ concentration, pH, the presence of PEG molecular crowders) was performed and the effect quantified in mismatched DNA compared to a canonical control sequence. Na+ concentration, pH and crowding agents have only a minimal effect on the backbone equilibrium (<5 % perturbation on backbone populations). But in the mismatched DNA, both K+ and Mg2+ shift the backbone equilibrium on both DNA strands but most significantly perturb the phosphates in proximity to the mismatch. This indicates a possible role of counterions in mismatch recognition or nucleotide flipping, and suggests knowledge of solutions conditions continue to be relevant for conformational processes.

Department(s)

Chemistry and Biochemistry

Document Type

Article

DOI

10.1016/j.bpc.2025.107548

Keywords

DNA phosphates, Mismatched DNA, NMR, Sample condition

Publication Date

2-1-2026

Journal Title

Biophysical Chemistry

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