Variability of the DNA Backbone Geometry in DNA–Protein Complexes: Experimental Data Analysis

• Published in: Journal of chemical information and modeling 2021-09, Vol.61 (9), p.4783-4794
• Main Authors: Strelnikov, Ivan A, Kovaleva, Natalya A, Zubova, Elena A
• Format: Article
• Language: English
• Subjects: Angles (geometry); Backbone; Bioinformatics; Data analysis; Histograms; NMR; Nuclear magnetic resonance; Nucleotides; Phosphates; Proteins; X-rays
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.1c00506

We have analyzed and compared the available experimental data (PDB) on the backbone geometry of the DNA in solution (NMR), in crystals (X-rays), and in complexes with proteins (X-rays and cryo-electron microscopy). The deoxyribose (pseudorotational angle τ0) and ε/ζ (BI–BII transition in phosphates) flexibilities are practically the same in the four samples. The α/γ mobility is minimal in crystalline DNA: on the histograms, there is one canonical and one noncanonical t/t peak. The α/γ mobility increases in DNA solutions (three more noncanonical peaks) and is maximal in DNA–protein complexes (another additional peak). On a large amount of data, we have confirmed that the three main degrees of freedom of the sugar-phosphate backbone are “orthogonal”: changes in any of the angles τ0, (ζ–ε), and (γ–α) occur, as a rule, at a constant (usually canonical) value of any other. In the DNA–protein complexes, none of the geometrical parameters commonly used to distinguish the A and B forms of DNA, except for Zp and its simpler analog Zp′, show an unambiguous correlation with τ0. Proteins, binding to DNA, in 59% of cases change the local shape of the helix up to the characteristic of the A-form without switching the deoxyribose conformation from south to north. However, we have found simple local characteristics of one nucleotide that correlate with the angles τ0 and (ζ–ε). These are the angles C3’C1’N* and C4’C3’P(2), respectively. They are orthogonal in DNA–protein complexes exactly as the pair τ0 and (ζ–ε). Most characteristics of DNA in complexes with proteins are the same in X-ray and in cryo-EM data, except for the histogram for the angle τ0. We offer a possible explanation for this difference. We also discuss the artifacts on the ε/ζ histogram for DNA in solutions caused by the currently used NMR refinement protocols.