MED-SuMoLig: a new ligand-based screening tool for efficient scaffold hopping

Area of Science:

• Computational chemistry
• Drug discovery
• Bioactive molecule identification

Background:

• Identifying selective small molecules is crucial for therapeutic development and life science research.
• Effective screening of large compound libraries is essential for discovering novel bioactive compounds.

Purpose of the Study:

• To develop and evaluate MED-SuMoLig, a novel ligand-based program for efficient screening of large compound collections.
• To assess the utility of MED-SuMoLig for 3D pharmacophore profiling and local atomic density computation.

Main Methods:

• MED-SuMoLig utilizes SMARTS-driven substructure searching for 3D pharmacophore profiling.
• The program computes local atomic density for comparing molecules.
• Performance was evaluated by screening 52 diverse active molecules against a library of 40,000 inactive compounds.

Main Results:

• MED-SuMoLig successfully recovered over half of the active molecules within the top 3% of the screened library across all tested targets.
• The program demonstrated superior enrichment rates compared to ChemMine and ROCS for CDK2 and Factor Xa.
• MED-SuMoLig performed comparably to ChemMine and ROCS for other tested targets (HIV-1 protease, neuraminidase, ribonuclease A, thymidine kinase).

Conclusions:

• MED-SuMoLig is an effective tool for the rapid identification of bioactive small molecules from large libraries.
• The program offers a competitive alternative to existing methods for drug discovery and chemical biology research.
• MED-SuMoLig's performance highlights its potential for advancing research in medicine and life sciences.