Database Commons

a catalog of worldwide biological databases

Non-canonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have garnered significant research interest because of their unique structural properties and biological activities. Thousands of small molecules targeting G4/iM structures have been developed for various chemical and biological applications. In response to the growing interest in G4-targeting ligands, we launched the first G4 Ligand Database (G4LDB) in 2013. Here, we introduce G4LDB 3.0 (http://www.g4ldb.com), an upgraded version featuring extensive enhancements in content and functionality. The new version includes over 4800 G4/iM ligands and approximately 51 000 activity entries. Key upgrades include advanced search capabilities, dynamic knowledge graphs, enhanced data visualization, along with a new dynamic analysis function that automatically displays ligand structure clustering results and chemical space distribution. With these updates, G4LDB 3.0 further evolves into a comprehensive resource and valuable research tool. The significant improvements address the increasing demand for efficient data handling and user experience, highlighting the critical role of G4LDB in advancing research on G-quadruplexes and i-motifs.

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4-ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.

The G-quadruplex ligands database (G4LDB, http://www.g4ldb.org) provides a unique collection of reported G-quadruplex ligands to streamline ligand/drug discovery targeting G-quadruplexes. G-quadruplexes are guanine-rich nucleic acid sequences in human telomeres and gene promoter regions. There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease. Ligands that affect the structure and activity of G-quadruplexes can shed light on the search for G-quadruplex-targeting drugs. Therefore, we built the G4LDB to (i) compile a data set covering various physical properties and 3D structure of G-quadruplex ligands; (ii) provide Web-based tools for G-quadruplex ligand design; and (iii) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G-quadruplexes. G4LDB currently contains >800?G-quadruplex ligands with ?4000 activity records, which, to our knowledge, is the most extensive collection of its kind. It offers a user friendly interface that can meet a variety of data inquiries from researchers. For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on. Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.