SPIDR: small-molecule peptide-influenced drug repurposing

Area of Science:

• Computational chemistry
• Drug discovery
• Pharmacology

Background:

• De novo drug design is expensive and time-consuming.
• Drug repurposing offers a cost-effective alternative by screening existing compounds.
• Software accelerates drug repurposing by screening chemical databases.

Purpose of the Study:

• To develop a computational method for identifying small-molecule drugs via peptide ligand conformational binding.
• To test the Small-molecule Peptide-Influenced Drug Repurposing (SPIDR) method using a specific peptide and receptor.

Main Methods:

• SPIDR utilizes a genetic algorithm to explore ligand binding domains.
• A library of 640,000 peptide analogs was screened against the α3β2-nicotinic acetylcholine receptor (nAChR).
• High-affinity peptides modeled small-molecule similarity searches in the PubChem Compound database using SimSearcher for efficient querying.

Main Results:

• SPIDR identified non-peptide drugs with nearly double the binding affinity of the native peptide.
• The method successfully explored conformational binding space for drug repurposing.

Conclusions:

• SPIDR has been integrated into DockoMatic v 2.1, enhancing its usability.
• DockoMatic provides a graphical interface for peptide screening, mapping, clustering, and database searching.
• DockoMatic is a valuable tool for researchers in drug design and repurposing.