Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight...

Area of Science:

• Computational chemistry
• Medicinal chemistry
• Drug discovery

Background:

• Virtual screening is crucial for identifying potential drug candidates.
• Pharmacophore-based virtual screening (PBVS) and docking-based virtual screening (DBVS) are two common computational approaches.
• Comparing their efficiencies is essential for optimizing drug discovery pipelines.

Purpose of the Study:

• To compare the efficiency of PBVS and DBVS methods.
• To evaluate their performance in retrieving active molecules against diverse protein targets.

Main Methods:

• Virtual screening was performed on small molecule datasets containing actives and decoys.
• Eight protein targets were used: ACE, AChE, AR, DacA, DHFR, ERalpha, HIV-pr, and TK.
• PBVS utilized the Catalyst program, while DBVS employed DOCK, GOLD, and Glide.

Main Results:

• PBVS showed higher enrichment factors than DBVS in fourteen out of sixteen virtual screening sets.
• The average hit rates for PBVS were significantly higher than DBVS at the top 2% and 5% ranks.
• PBVS demonstrated superior performance in identifying active compounds across the tested targets.

Conclusions:

• PBVS is a more effective method than DBVS for retrieving active compounds.
• PBVS is a powerful tool that can significantly aid in the drug discovery process.