A unified dinucleotide alphabet describing both RNA and DNA structures

Abstract

By analyzing almost 120 000 dinucleotides in over 2000 nonredundant nucleic acid crystal structures, we define 96+1 diNucleotide Conformers, NtCs, which describe the geometry of RNA and DNA dinucleotides. NtC classes are grouped into 15 codes of the structural alphabet CANA (Conformational Alphabet of Nucleic Acids) to simplify symbolic annotation of the prominent structural features of NAs and their intuitive graphical display. The search for nontrivial patterns of NtCs resulted in the identification of several types of RNA loops, some of them observed for the first time. Over 30% of the nearly six million dinucleotides in the PDB cannot be assigned to any NtC class but we demonstrate that up to a half of them can be re-refined with the help of proper refinement targets. A statistical analysis of the preferences of NtCs and CANA codes for the 16 dinucleotide sequences showed that neither the NtC class AA00, which forms the scaffold of RNA structures, nor BB00, the DNA most populated class, are sequence neutral but their distributions are significantly biased. The reported automated assignment of the NtC classes and CANA codes available at dnatco.org provides a powerful tool for unbiased analysis of nucleic acid structures by structural and molecular biologists.

Structural variability of CG-rich DNA 18-mers accommodating double T–T mismatches

“…The dinucleotide conformational (NtC) classes (Schneider et al, 2018;Č erný, Božíková , Svoboda et al, 2020) allow the objective classification of DNA and RNA geometries. The classification is automated and is available at the web site https://dnatco.datmos.org/ (Č erný et al, 2016), where DNA-or RNA-containing structures in mmCIF or PDB format are dissected into dinucleotide blocks that are then assigned to NtC classes, with a related goodness-of-fit measure (confal) and several other characteristics.…”

“…The observed electron density in the T10-G11-C12 region was not of sufficient quality to guide manual model building. This fact was reflected by a poor overlap between the manually fitted geometries of the dinucleotides T10-G11 and G11-C12 and the geometry of any known NtC class (Schneider et al, 2018;Č erný, Božíková , Svoboda et al, 2020). An in-depth geometric analysis of these dinucleotides in the pre-final coordinates indicated the possibility of improving their geometric fit to the target NtC geometries.…”

“…The fit was calculated as the root-mean-square deviation (r.m.s.d. ) between the investigated dinucleotide and the geometrically closest dinucleotide from the ensemble of dinucleotides defining the NtC classes (Č erný, Božíková , Svoboda et al, 2020). In the following step, we measured the real-space correlation coefficient (RSCC; Authier & Chapuis, 2014) for the investigated mismatched dinucleotides.…”

“…Scattergrams showing the relationship between the fit to electron density (measured as the real-space correlation coefficient; RSCC) and the geometric fit between the dinucleotide geometry and the geometrically closest dinucleotide in the 'golden set', an ensemble of dinucleotides defining the NtC classes (r.m.s.d.) (Č erný, Božíková , Svoboda et al, 2020). The data were calculated for dinucleotides containing at least one base forming a noncanonical base pair.…”

“…Therefore, we further analyzed the geometries of dinucleotides containing T-T and other mismatches in other crystal structures and observed that they mostly adopt the conformations known for Watson-Crick paired dinucleotides so that they do not disrupt the regular double-helical arrangement. The analysis of the mismatched segments from the database as well as the refinement of our crystal structures benefited from the knowledge of the nucleic acid dinucleotide (NtC) classes (Schneider et al, 2018;Č erný, Božíková , Svoboda et al, 2020) and the tools available at the web server https://dnatco.datmos.org/ (Č erný et al, 2016), showing the potential of the NtC classification for an automated, strictly geometric analysis of nucleic acids.…”