Calculation of binding energy using BLYP/MM for the HIV-1 integrase complexed with the S-1360 and two analogues

Bioorg Med Chem. 2007 Jun 1;15(11):3818-24. doi: 10.1016/j.bmc.2007.03.027. Epub 2007 Mar 13.


Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. S-1360 is a potent and selective inhibitor of HIV-1 IN. In this work, we have carried out molecular dynamics (MD) simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach, to determine the protein-ligand interaction energy for S-1360 and two analogues. Analysis of the MD trajectories reveals that the strongest protein-inhibitor interactions, observed in the three studied complexes, are established with Lys-159 residue and Mg(2+) cation. Calculations of binding energy using BLYP/MM level of theory reveal that there is a direct relationship between this theoretical computed property and the experimental determined anti-HIV activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Crystallography, X-Ray
  • Furans / chemistry*
  • HIV Integrase / chemistry*
  • HIV Integrase Inhibitors / chemistry*
  • Humans
  • Lysine / chemistry
  • Magnesium / chemistry
  • Models, Chemical*
  • Propane / analogs & derivatives*
  • Propane / chemistry
  • Protein Conformation
  • Pyrroles / chemistry*
  • Structure-Activity Relationship
  • Triazoles / chemistry*


  • 1-(5-((4-fluorophenyl)methyl)pyrrol-2-yl)-3-hydroxy-3-(2H-1,2,4-triazol-3-yl)prop-2-en-1-one
  • Furans
  • HIV Integrase Inhibitors
  • Pyrroles
  • S 1360
  • Triazoles
  • HIV Integrase
  • Magnesium
  • Lysine
  • Propane