Fig 1.
Example polyadic motifs of different orders and their schematic representations: (A) pentad (5 nucleotides), (B) hexad (6 nucleotides), (C) heptad (7 nucleotides), and (D) octad (8 nucleotides).
In the 3D models (top row), nucleotides forming the polyads are shown in color, coded by nucleotide type: green for guanine, blue for uracil or thymine, and red for adenine. Green thus highlights the guanine tetrad core.
Fig 2.
LinkTetrado flowchart.
Fig 3.
Geometric definitions used in the evaluation of the candidate nucleotide.
The schematic illustrates the vectors and reference points employed in (A) Criterion 1 (connectivity), (B) Criterion 2 (tilt, defined by the angle between the candidate and tetrad base normal vectors), (C) Criterion 3 (distance, measured between the candidate and the tetrad centroid), and (D) Criterion 4 (height difference, calculated as the projection of candidate–centroid vectors onto tetrad base normals).
Fig 4.
(A) The number of structures containing polyadic motifs, grouped by motif type, and the total number of motifs of each type detected by LinkTetrado.
(B) Distribution of structures containing only one or two polyadic motifs of a given type. Each bar shows both the percentage and the absolute number of structures.
Fig 5.
Dimeric DNA structure (PDB ID: 1EEG; [25]) shown as (A) a cartoon model visualized in PyMOL [26] and (B) a layer diagram generated with DrawTetrado [27].
The G4 helix is colored green and contains two (A:)G:G:G:G(:A) hexads. Adenines that interact with tetrad-forming guanines are highlighted in red.
Fig 6.
Confirmation of polyad formation using NMR restraints for the dimeric RNA G-quadruplex structure (PDB ID: 2RQJ).
(A) Schematic representation of distance restraints between exchangeable protons and their partners in residues G1 and A3, which form a sheared G:A base pair underlying hexad formation. (B) Selected lines from the 2rqj.mr restraint file that report on the in-plane position of residue A3 and the formation of hydrogen bonds between G1 and A3. For clarity, only restraints involving exchangeable protons are shown. The lines in (B) are shaded in colors that correspond to the interaction paths marked in (A), indicating which restraint supports which structural feature.
Fig 7.
False positives identified by LinkTetrado in structures with PDB IDs (A) 5LIG, (B) 1NYD, (C) 2KYP, (D) 6H5R, (E) 4R44, and (F) 6W9P.
Top and side views of each structure illustrate the position of the hypothetical polyad residue relative to the G-quartet plane. Hydrogen bonds detected using molecular visualization software are shown in black. Residues are color-coded: green for guanine, red for adenine, blue for thymine, and yellow for cytosine.