Blind prediction of HIV integrase binding from the SAMPL4 challenge

J Comput Aided Mol Des. 2014 Apr;28(4):327-45. doi: 10.1007/s10822-014-9723-5. Epub 2014 Mar 5.


Here, we give an overview of the protein-ligand binding portion of the Statistical Assessment of Modeling of Proteins and Ligands 4 (SAMPL4) challenge, which focused on predicting binding of HIV integrase inhibitors in the catalytic core domain. The challenge encompassed three components--a small "virtual screening" challenge, a binding mode prediction component, and a small affinity prediction component. Here, we give summary results and statistics concerning the performance of all submissions at each of these challenges. Virtual screening was particularly challenging here in part because, in contrast to more typical virtual screening test sets, the inactive compounds were tested because they were thought to be likely binders, so only the very top predictions performed significantly better than random. Pose prediction was also quite challenging, in part because inhibitors in the set bind to three different sites, so even identifying the correct binding site was challenging. Still, the best methods managed low root mean squared deviation predictions in many cases. Here, we give an overview of results, highlight some features of methods which worked particularly well, and refer the interested reader to papers in this issue which describe specific submissions for additional details.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Catalytic Domain
  • Computer Simulation
  • Computer-Aided Design
  • Drug Design
  • HIV / enzymology*
  • HIV Infections / drug therapy
  • HIV Infections / enzymology
  • HIV Infections / virology
  • HIV Integrase / chemistry
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Models, Statistical
  • Protein Binding


  • HIV Integrase Inhibitors
  • HIV Integrase