AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology and Drug Discovery
• Bioinformatics and Computational Biology

Background:

• Allosteric regulation is crucial for biological processes, human diseases, and drug discovery.
• Identifying allosteric modulators is essential for understanding biological mechanisms and developing novel therapeutics.

Purpose of the Study:

• To present AlloFinder, an interactive platform for identifying potential endogenous and exogenous allosteric modulators.
• To map the human allosterome, including allosteric sites and modulators.
• To facilitate the discovery of allosteric modulators for metabolic enzymes and disease-related targets.

Main Methods:

• Integrated approach combining allosteric site identification, screening, and scoring of modulator-protein complexes.
• Allosterome mapping analysis of predicted allosteric sites and modulators within the human proteome.
• Validation using a case study on signal transduction and activation of transcription 3 (STAT3).

Main Results:

• AlloFinder successfully identified known allosteric metabolites and exogenous modulators for established allosteric proteins.
• The platform demonstrated effectiveness in identifying allosteric metabolites for metabolic enzymes.
• Case study on STAT3 validated AlloFinder's capability to discover allosteric modulators, confirmed by experimental data.

Conclusions:

• AlloFinder is a valuable web server for exploring allosteric regulation mechanisms between metabolites and enzymes.
• The platform is expected to accelerate the discovery of allosteric drugs for various human diseases.
• AlloFinder is freely accessible, promoting research in allosteric regulation and drug development.