WebTetrado: a webserver to explore quadruplexes in nucleic acid 3D structures

Abstract

Quadruplexes are four-stranded DNA/RNA motifs of high functional significance that fold into complex shapes. They are widely recognized as important regulators of genomic processes and are among the most frequently investigated potential drug targets. Despite interest in quadruplexes, few studies focus on automatic tools that help to understand the many unique features of their 3D folds. In this paper, we introduce WebTetrado, a web server for analyzing 3D structures of quadruplex structures. It has a user-friendly interface and offers many advanced features, including automatic identification, annotation, classification, and visualization of the motif. The program applies to the experimental or in silico generated 3D models provided in the PDB and PDBx/mmCIF files. It supports canonical G-quadruplexes as well as non-G-based quartets. It can process unimolecular, bimolecular, and tetramolecular quadruplexes. WebTetrado is implemented as a publicly available web server with an intuitive interface and can be freely accessed at https://webtetrado.cs.put.poznan.pl/.

Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling

“…61–66 For instance, hybrid structures where three strands are stacking anti – anti and one strand is stacking syn – syn , result in ECD spectra characterized by a positive peak at 260 nm (with a slight shoulder at 290 nm) and negative band at 240 nm, which generally indicate predominant parallel G4s. 61 As can be verified by processing the representative snapshot structures (available in the ESI†) in webservers like ASC-G4 or WebTetrado, 67,68 our optimized hybrid G4 structure is characterized by the following configuration: G1–G2 anti – anti ; G9–G8 syn – syn ; G13–G14 anti – anti ; G19–G20 anti – anti . This is exactly the case when hybrid structures give ECD spectra similar to the one experimentally recorded.…”

Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS

“…The bimolecular parallel G4 of d(AAGGG) 2 AA contains three G-tetrads with every two layers exhibiting extensive base-base stackings (Figure 3B ). More detailed structural features including the twist and rise between every two adjacent G-tetrads were analyzed using the WebTetrado tool ( 43 ) and shown in Supplementary Figure S12 . To connect the three G-tetrad layers, the phosphodiester backbones of A6 a /A6 b and A7 a /A7 b were twisted, and this is consistent with the weak NOEs of G5 H1′-A6 H8, A6 H1′-A7 H8 and A7 H1′-G8 H8 (Figure 2A ).…”