Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina

PLoS One. 2010 Aug 4;5(8):e11955. doi: 10.1371/journal.pone.0011955.


Background: The AutoDock family of software has been widely used in protein-ligand docking research. This study compares AutoDock 4 and AutoDock Vina in the context of virtual screening by using these programs to select compounds active against HIV protease.

Methodology/principal findings: Both programs were used to rank the members of two chemical libraries, each containing experimentally verified binders to HIV protease. In the case of the NCI Diversity Set II, both AutoDock 4 and Vina were able to select active compounds significantly better than random (AUC = 0.69 and 0.68, respectively; p<0.001). The binding energy predictions were highly correlated in this case, with r = 0.63 and iota = 0.82. For a set of larger, more flexible compounds from the Directory of Universal Decoys, the binding energy predictions were not correlated, and only Vina was able to rank compounds significantly better than random.

Conclusions/significance: In ranking smaller molecules with few rotatable bonds, AutoDock 4 and Vina were equally capable, though both exhibited a size-related bias in scoring. However, as Vina executes more quickly and is able to more accurately rank larger molecules, researchers should look to it first when undertaking a virtual screen.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Area Under Curve
  • Drug Evaluation, Preclinical / methods*
  • Fluorometry
  • HIV Protease / chemistry
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / metabolism
  • HIV Protease Inhibitors / pharmacology*
  • Ligands
  • Models, Molecular
  • National Cancer Institute (U.S.)
  • Protein Conformation
  • ROC Curve
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Software*
  • Thermodynamics
  • United States
  • User-Computer Interface*


  • HIV Protease Inhibitors
  • Ligands
  • Small Molecule Libraries
  • HIV Protease