Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries

Comb Chem High Throughput Screen. 2009 May;12(4):344-57. doi: 10.2174/138620709788167944.


Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Artificial Intelligence*
  • Computer Simulation
  • Drug Evaluation, Preclinical / methods*
  • Drug Interactions
  • Ligands*
  • Pharmaceutical Preparations / chemical synthesis
  • Pharmaceutical Preparations / chemistry*
  • Small Molecule Libraries*
  • Structure-Activity Relationship


  • Ligands
  • Pharmaceutical Preparations
  • Small Molecule Libraries