HPPD: ligand- and target-based virtual screening on a herbicide target.

Area of Science:

• Agrochemical science
• Computational chemistry
• Drug discovery

Background:

• Hydroxyphenylpyruvate dioxygenase (HPPD) is a validated target for bleaching herbicides.
• HPPD inhibitors are commercially successful in the agrochemical market.
• Syngenta has extensive experience in HPPD inhibitor research.

Purpose of the Study:

• To validate diverse ligand- and target-based virtual screening methods.
• To identify novel compounds with HPPD inhibitory properties.
• To assess virtual screening utility and scaffold-hopping capabilities.

Main Methods:

• Ligand-based methods: 2D fingerprints, 3D shape (ROCS, EON, Phase-shape), pharmacophore (Phase).
• Target-based methods: Glide, Gold.
• Evaluation of virtual screening utility and scaffold-hopping ability.

Main Results:

• Successful identification of compounds with HPPD inhibitory properties.
• Assessment of the performance of various virtual screening tools.
• Comparison of virtual screening in agrochemical versus pharmaceutical contexts.

Conclusions:

• Virtual screening is a valuable approach for discovering HPPD inhibitors.
• Specific considerations are crucial for agrochemical virtual screening campaigns.
• The study provides insights into optimizing virtual screening for herbicide discovery.