Protein Preparation Automatic Protocol for High-Throughput Inverse Virtual Screening: Accelerating the Target...

Area of Science:

• Computational chemistry
• Drug discovery
• Bioinformatics

Background:

• Structure-based virtual screening is common in drug discovery.
• Identifying targets for bioactive molecules with unknown targets or side effects is crucial.
• Inverse virtual screening (IVS) can identify molecular targets but requires extensive protein panel preparation.

Purpose of the Study:

• To develop and validate an automated workflow for preparing protein panels for IVS.
• To expedite the identification of interacting targets for bioactive compounds.
• To facilitate drug repurposing and polypharmacology studies.

Main Methods:

• Developed an automated workflow for preparing protein panels from the Protein Data Bank.
• Applied the workflow to viral (628 proteins) and transferase (2789 proteins) protein panels.
• Performed large-scale inverse virtual screening using docked compounds and validated binding with surface plasmon resonance.

Main Results:

• The automated workflow significantly reduces time and effort in protein panel preparation.
• Inverse virtual screening identified Tankyrase 2 (PARP 5b) as the preferred target for tested compounds.
• Predicted interactions were successfully validated through experimental surface plasmon resonance.

Conclusions:

• The automated protocol enables rapid identification of interacting targets for bioactive compounds.
• This approach enhances the efficiency of drug repurposing and polypharmacology investigations.
• The workflow supports high-throughput virtual screening by streamlining panel preparation.