Multiple target screening method for robust and accurate in silico ligand screening.

Area of Science:

• Computational chemistry
• Cheminformatics
• Drug discovery

Background:

• In silico screening methods are crucial for identifying potential drug candidates.
• Existing methods may lack robustness and efficiency in identifying hits across multiple targets.

Purpose of the Study:

• To develop and validate a novel in silico multiple target screening (MTS) method.
• To assess the robustness of the MTS method across different scoring systems.

Main Methods:

• Developed an MTS method based on multi-receptor versus multi-ligand docking affinity matrices.
• Applied the method to screen 142 receptors against 142 compounds using the Sievgene docking program.
• Introduced and evaluated two new scoring functions: DeltaG score and hit-optimized score.

Main Results:

• The developed MTS method demonstrated a high hit ratio compared to uniform sampling.
• The MTS method showed greater robustness across different scoring systems (Sievgene, DeltaG, hit-optimized) than the multiple active-site correction scoring method.
• New scoring functions (DeltaG and hit-optimized) were prepared and tested.

Conclusions:

• The novel in silico multiple target screening (MTS) method is effective and robust for identifying potential drug candidates.
• The MTS method offers an improvement over existing techniques for virtual screening against multiple targets.
• The developed scoring functions contribute to the enhanced performance of the MTS approach.