Classification of g-quadruplex DNA on the basis of the quadruplex twist angle and planarity of g-quartets

Abstract

The present work is devoted to the analysis of the G-quadruplex DNA structure using the bioinformatics method. The interest towards quadruplex DNAs is determined by their involvement in the functioning of telomeres and onco-promoters as well as by the possibility to create on their basis aptamers and nanostructures. Here, we present an algorithm for a general analysis of the polymorphism of the G-quadruplex structure from the data bank PDB using original parameters. 74 structures were grouped according to the following parameters: the number of DNA strands, the number of G-quartets, and the location and orientation of the connecting loops. Two quantitative parameters were used to describe the quadruplex structure: the twist angle between two adjacent quartets (analogous to that for the complementary pair in the duplex DNA) and the quartet planarity (an original parameter). The distribution patterns of these values are specific for each group of quadruplex structures and are dependent upon the type of connecting loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel quadruplex was used as a comparison template. The lateral loops introduce the strongest distortion into the structure of quadruplexes: the values of the twist angles are the lowest and are not typical for the other quadruplex groups. The loops of the diagonal type introduce much weaker deformation into quadruplexes; the structures with propeller loops are characterized by the optimum geometry of G-quartets. Hence, the correlation between the twist angle and the tension in the structure of quadruplex DNA is revealed.

Keywords: G-quadruplex; G-quartet; loops; structure; twist angle.

Fig. 1

Scheme of G-quartet. Four guanine residues form a square coplanar structure, where each nucleic acid base is a donor and acceptor of a hydrogen bond: N1 and N2 from one side of the heterocycle, O6 and N7 from the other side of the guanosine involved in formation of 8 hydrogen bonds in one quartet. Sugar-phosphate backbone of nucleic acids is denoted as R.

Fig. 2

Four-stranded intermolecular parallel G-quadruplex.

Fig. 3

Folding of a DNA strand into a monomolecular G-quadruplex with three G-quartets. Two variants of oligonucleotide d(AGGG(TTAGGG) ₃ ) differ from each other in the direction of the polynucleotide chain in different strands of the quadruplex. Left: topology with loops of lateral and diagonal type [23]; right: topology with strand-reversal loops of propeller type [24].

Fig. 4

Definition of the measured parameters. Left: Definition of the quadruplex twist angle. C1’ atoms are shown as spheres. Right: relative positions of two tetragons: the outer, formed by N9 atoms, and the inner, formed by O6 atoms. If the planarity of the quartet is disturbed, then the inner tetragon leaves the quartet plane. Distance between the centers of mass of the inner and outer tetragons is the numeric parameter of planarity deviation.

Fig. 5

Structural organization and geometrical features of the first group of structures.

Fig. 6

Structural organization and geometrical features of the second and third groups of structures.

Fig. 7

Structural organization and geometrical features of the fourth group of structures.

Fig. 8

Structural organization and geometrical features of the fifth group of structures.

Fig. 9

Structural organization and geometrical features of the sixth and seventh groups of structures.

Fig. 10

Structural organization and geometrical features of the eight group of structures.