Protein-DNA interactions in disease and drug discovery

Area of Science:

• Molecular Biology
• Genetics
• Pharmacology

Background:

• Protein-DNA interactions (PDIs) are essential biological processes fundamental to all organisms.
• Dysregulation of PDIs is implicated in disease onset, progression, and severity.
• Targeting PDIs for therapeutic intervention presents challenges due to factors like DNA backbone interactions.

Purpose of the Study:

• To review the role of PDIs in human transcription, replication-and-repair, and genome organization.
• To highlight PDIs as viable therapeutic targets in various diseases.
• To survey drug discovery efforts and computational methods, including AI, for targeting PDIs.

Main Methods:

• Literature review of PDIs in human biology and disease.
• Compilation of PDIs targeted by drugs in clinical trials or approved.
• Review of computational and AI-based approaches for PDI drug discovery.

Main Results:

• Misregulation of PDIs in transcription, replication-and-repair, and genome organization is linked to diseases.
• A growing number of PDIs and associated drugs have reached clinical trial or approval stages.
• Computational methods, particularly AI, are accelerating PDI drug discovery.

Conclusions:

• PDIs, despite historical challenges, are increasingly recognized as druggable targets.
• The review demonstrates the growing potential and success of targeting PDIs for therapeutic benefit.
• The time is opportune to leverage PDIs as effective therapeutic targets, supported by advancing methodologies.