Discovery of a novel binding trench in HIV integrase

J Med Chem. 2004 Apr 8;47(8):1879-81. doi: 10.1021/jm0341913.

Abstract

Docking of the 5CITEP inhibitor to snapshots of a 2 ns HIV-1 integrase MD trajectory indicated a previously uncharacterized trench adjacent to the active site that intermittently opens. Further docking studies of novel ligands with the potential to bind to both regions showed greater selective affinity when able to bind to the trench. Our ranking of ligands is open to experimental testing, and our approach suggests a new target for HIV-1 therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • HIV Integrase / chemistry*
  • HIV Integrase / metabolism
  • Indoles / chemistry
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Naphthalenes / chemistry
  • Protein Binding
  • Structure-Activity Relationship
  • Tetrazoles / chemistry

Substances

  • 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)propenone
  • Indoles
  • Ligands
  • Naphthalenes
  • Tetrazoles
  • HIV Integrase