RNAhugs web server for customized 3D RNA structure alignment.

Alignment of 3D molecular structures involves overlaying their sets of atoms in space in such a way as to minimize the distance between the corresponding atoms. The purpose of this procedure is usually to analyze and assess structural similarity on a global (e.g. evaluating predicted 3D models and clustering structures) or a local level (e.g. searching for common substructures). Although the idea of alignment is simple, combinatorial algorithms that implement it require considerable computational resources, even when processing relatively small structures. In this paper, we introduce RNAhugs, a web server for custom and flexible alignment of 3D RNA structures. Using two efficient heuristics, GEOS and GENS, it finds the longest corresponding fragments within 3D structures that may differ in sizes-given in the PDB or PDBx/mmCIF formats-that manage to align with user-specified accuracy (i.e. with an RMSD not exceeding a cutoff value given as an input parameter). A distinctive advantage of the system lies in its ability to process multi-model files and compare the results of 1-25 alignments in a single task. RNAhugs has an intuitive interface and is publicly available at https://rnahugs.cs.put.poznan.pl/.

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

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/.

High-quality, customizable heuristics for RNA 3D structure alignment.

MOTIVATION: Tertiary structure alignment is one of the main challenges in the computer-aided comparative study of molecular structures. Its aim is to optimally overlay the 3D shapes of two or more molecules in space to find the correspondence between their nucleotides. Alignment is the starting point for most algorithms that assess structural similarity or find common substructures. Thus, it has applications in solving a variety of bioinformatics problems, e.g. in the search for structural patterns, structure clustering, identifying structural redundancy, and evaluating the prediction accuracy of 3D models. To date, several tools have been developed to align 3D structures of RNA. However, most of them are not applicable to arbitrarily large structures and do not allow users to parameterize the optimization algorithm. RESULTS: We present two customizable heuristics for flexible alignment of 3D RNA structures, geometric search (GEOS), and genetic algorithm (GENS). They work in sequence-dependent/independent mode and find the suboptimal alignment of expected quality (below a predefined RMSD threshold). We compare their performance with those of state-of-the-art methods for aligning RNA structures. We show the results of quantitative and qualitative tests run for all of these algorithms on benchmark sets of RNA structures. AVAILABILITY AND IMPLEMENTATION: Source codes for both heuristics are hosted at https://github.com/RNApolis/rnahugs.

ONQUADRO: a database of experimentally determined quadruplex structures.

ONQUADRO is an advanced database system that supports the study of the structures of canonical and non-canonical quadruplexes. It combines a relational database that collects comprehensive information on tetrads, quadruplexes, and G4-helices; programs to compute structure parameters and visualise the data; scripts for statistical analysis; automatic updates and newsletter modules; and a web application that provides a user interface. The database is a self-updating resource, with new information arriving once a week. The preliminary data are downloaded from the Protein Data Bank, processed, annotated, and completed. As of August 2021, ONQUADRO contains 1,661 tetrads, 518 quadruplexes, and 30 G4-helices found in 467 experimentally determined 3D structures of nucleic acids. Users can view and download their description: sequence, secondary structure (dot-bracket, classical diagram, arc diagram), tertiary structure (ball-and-stick, surface or vdw-ball model, layer diagram), planarity, twist, rise, chi angle (value and type), loop characteristics, strand directionality, metal ions, ONZ, and Webba da Silva classification (the latter by loop topology and tetrad combination), origin structure ID, assembly ID, experimental method, and molecule type. The database is freely available at https://onquadro.cs.put.poznan.pl/. It can be used on both desktop computers and mobile devices.

DrawTetrado to create layer diagrams of G4 structures.

MOTIVATION: Quadruplexes are specific 3D structures found in nucleic acids. Due to the exceptional properties of these motifs, their exploration with the general-purpose bioinformatics methods can be problematic or insufficient. The same applies to visualizing their structure. A hand-drawn layer diagram is the most common way to represent the quadruplex anatomy. No molecular visualization software generates such a structural model based on atomic coordinates. RESULTS: DrawTetrado is an open-source Python program for automated visualization targeting the structures of quadruplexes and G4-helices. It generates static layer diagrams that represent structural data in a pseudo-3D perspective. The possibility to set color schemes, nucleotide labels, inter-element distances or angle of view allows for easy customization of the output drawing. AVAILABILITY AND IMPLEMENTATION: The program is available under the MIT license at https://github.com/RNApolis/drawtetrado.

RNApdbee 2.0: multifunctional tool for RNA structure annotation.

In the field of RNA structural biology and bioinformatics, an access to correctly annotated RNA structure is of crucial importance, especially in the secondary and 3D structure predictions. RNApdbee webserver, introduced in 2014, primarily aimed to address the problem of RNA secondary structure extraction from the PDB files. Its new version, RNApdbee 2.0, is a highly advanced multifunctional tool for RNA structure annotation, revealing the relationship between RNA secondary and 3D structure given in the PDB or PDBx/mmCIF format. The upgraded version incorporates new algorithms for recognition and classification of high-ordered pseudoknots in large RNA structures. It allows analysis of isolated base pairs impact on RNA structure. It can visualize RNA secondary structures-including that of quadruplexes-with depiction of non-canonical interactions. It also annotates motifs to ease identification of stems, loops and single-stranded fragments in the input RNA structure. RNApdbee 2.0 is implemented as a publicly available webserver with an intuitive interface and can be freely accessed at http://rnapdbee.cs.put.poznan.pl/.

New algorithms to represent complex pseudoknotted RNA structures in dot-bracket notation.

Motivation: Understanding the formation, architecture and roles of pseudoknots in RNA structures are one of the most difficult challenges in RNA computational biology and structural bioinformatics. Methods predicting pseudoknots typically perform this with poor accuracy, often despite experimental data incorporation. Existing bioinformatic approaches differ in terms of pseudoknots' recognition and revealing their nature. A few ways of pseudoknot classification exist, most common ones refer to a genus or order. Following the latter one, we propose new algorithms that identify pseudoknots in RNA structure provided in BPSEQ format, determine their order and encode in dot-bracket-letter notation. The proposed encoding aims to illustrate the hierarchy of RNA folding. Results: New algorithms are based on dynamic programming and hybrid (combining exhaustive search and random walk) approaches. They evolved from elementary algorithm implemented within the workflow of RNA FRABASE 1.0, our database of RNA structure fragments. They use different scoring functions to rank dissimilar dot-bracket representations of RNA structure. Computational experiments show an advantage of new methods over the others, especially for large RNA structures. Availability and implementation: Presented algorithms have been implemented as new functionality of RNApdbee webserver and are ready to use at http://rnapdbee.cs.put.poznan.pl. Contact: mszachniuk@cs.put.poznan.pl. Supplementary information: Supplementary data are available at Bioinformatics online.