InterLig

InterLig performs ligand-based virtual screening by using topologically independent structural alignments and 3D similarity to compare and superpose small molecules for scaffold hopping and identification of functional analogs when the protein target is unknown.

Key Features:

• Topologically Independent Alignments: Aligns molecular structures using topological relationships between atoms independent of initial spatial configuration to enable comparisons across different chemical scaffolds.
• 3D-Based Similarity Methods: Uses three-dimensional structural data and molecular superposition to highlight functional similarity beyond geometric congruence.
• Benchmark Performance: Demonstrated improved performance in comparative studies on standard 3D virtual screening benchmarks relative to other methods.

Scientific Applications:

• Ligand-based virtual screening: Screens large chemical libraries using known active ligands to identify new candidate molecules without requiring a protein structure.
• Scaffold hopping and lead identification: Identifies structurally diverse compounds that share functional similarity with known actives to expand chemical diversity of leads.
• Target-agnostic hit finding: Facilitates hit discovery in early-stage drug discovery when the molecular target is unknown.

Methodology:

InterLig applies topologically independent structural alignments based on atomic connectivity together with three-dimensional similarity and molecular superposition of small molecules.