A DNA structural alphabet provides new insight into DNA flexibility

Abstract

DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. To identify the DNA structural polymorphisms that are possible in such adaptations, the dinucleotide structures of 60 000 DNA steps from sequentially nonredundant crystal structures were classified and an automated protocol assigning 44 distinct structural (conformational) classes called NtC (for Nucleotide Conformers) was developed. To further facilitate understanding of the DNA structure, the NtC were assembled into the DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the projection of CANA onto the graphical representation of the molecular structure was proposed. The NtC classification was used to define a validation score called confal, which quantifies the conformity between an analyzed structure and the geometries of NtC. NtC and CANA assignment were applied to analyze the structural properties of typical DNA structures such as Dickerson-Drew dodecamers, guanine quadruplexes and structural models based on fibre diffraction. NtC, CANA and confal assignment, which is accessible at the website https://dnatco.org, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Acta_Cryst_D:2.

X‐ray Crystal Structures Show DNA Stacking Advantage of Terminal Nitrile Substitution in Ru‐dppz Complexes

“…At the intercalation cavity there is evidenceo fb ackbone disorder,a nd the phosphate group of residue G10 was modelleda samixture of B I and B II conformations. [34] As we have previously seen with the unsubstituted dppz and this sequence, [25] there is ar eversal in the conformation of the terminal guanine base G10, so that it stacksi nasyn conformationw ith the negative, and normally major groove face of the guanine stacked over the pyrazine ring, and aligning the 2-NH 2 vector direction of the guanine with one of the ligand CN groups. Furtherd etails of map quality and water structure are shown in FiguresS9a nd S10.…”

“…Analysis of DNA dihedral angles was performed using DNATCO. [34] Structural diagrams were created using PyMol (Schrçdinger).…”

Enriched Conformational Sampling of DNA and Proteins with a Hybrid Hamiltonian Derived from the Protein Data Bank

“…A smaller fraction of approximately 20% of the steps have B-A conformations, while 15% are in BII or mixed BI/BII configurations. The smallest fraction, 10%, of the dinucleotide steps adopt A and A-to-B forms [ 68 ]. Analogous to the broadly accepted structural heterogeneity of proteins, especially intrinsically disordered peptides, we observe that the DNA dodecamer accesses a larger number of classes, ranging from the A to the B form, which we characterized by a classification using the structural alphabet of DNA.…”

“…The structural datasets demonstrate the structural variability of DNA and proteins, knowledge which has been necessary for understanding how DNA and proteins adopt their structures upon binding to ligands or other biomolecules in signaling processes. For example, it has been shown that DNA can adopt a large variety of structural conformers in addition to the canonical ’B’ form found by Watson and Crick [ 65 ], as defined in the structural alphabet of DNA [ 65 , 66 , 67 , 68 ]. The variety of possible structures ranges from double to triple and quadruple helices [ 69 , 70 ], DNA junctions, as well as parallel helices and hairpins [ 71 , 72 ].…”

Structural alphabets for conformational analysis of nucleic acids available at dnatco.datmos.org

“…The assignment of DNA conformations was introduced as a web server that is currently available at https://dnatco.datmos.org/ v2 (Č erný et al, 2016). The evolved description of DNA conformations was based on a nine-dimensional space of parameters containing seven backbone torsions and two torsion angles around glycosidic bonds within a DNA dinucleotide step (Schneider et al, 2018). This approach has also successfully been applied to the identification of the key structural differences between a DNA interacting with regulatory proteins and in the nucleosome core particle, explaining the structural details of different mechanisms of DNA bending (Schneider et al, 2017).…”