G-quadruplex virtual drug screening: A review.

Area of Science:

• Biochemistry and Bioinformatics
• Drug Discovery and Medicinal Chemistry

Background:

• G-quadruplexes (G4s) are increasingly recognized as key regulators of biological processes, including DNA replication, transcription, and splicing.
• Their structural diversity and prevalence in cancer-associated gene promoters make them attractive targets for therapeutic intervention.
• Existing atomic structures of DNA and RNA G-quadruplexes facilitate computational drug design.

Purpose of the Study:

• To review virtual drug discovery approaches for G-quadruplexes over the past decade.
• To introduce effective virtual screening platforms for G4 ligand identification.
• To provide best practices for future G-quadruplex virtual screening (G4 VS) campaigns.

Main Methods:

• Literature review of G-quadruplex virtual drug discovery campaigns.
• Identification and categorization of relevant in silico screening platforms.
• Analysis of successful and unsuccessful G4 VS strategies.

Main Results:

• The past decade has seen significant advancements in computational methods for G-quadruplex drug discovery.
• Various virtual screening platforms have been developed and applied to identify novel G4 stabilizing ligands.
• Key structural features and screening parameters influencing campaign success have been identified.

Conclusions:

• Virtual drug discovery is a powerful and evolving strategy for developing G-quadruplex-targeting therapeutics.
• Standardized best practices are essential for optimizing future G4 VS campaigns and accelerating the discovery of novel drug candidates.
• Continued integration of structural biology and computational chemistry will drive innovation in G-quadruplex-based drug development.