3D QSAR CoMFA/CoMSIA, molecular docking and molecular dynamics studies of fullerene-based HIV-1 PR inhibitors

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6283-9. doi: 10.1016/j.bmcl.2008.09.107. Epub 2008 Oct 8.

Abstract

For the first time, a set of experimentally reported [60] fullerene derivatives were subjected to the 3D-QSAR/CoMFA and CoMSIA studies. The aim of this study is to propose a series of novel [60] fullerene-based inhibitors with optimal binding affinity for the HIV-1 PR enzyme. The position of the template molecule at the cavity of HIV-1 PR was optimized and 3D QSAR models were developed. Relative contributions of steric/electrostatic fields of the 3D-QSAR/CoMFA and CoMSIA models have shown that steric effects govern the bioactivity of the compounds, but electrostatic interactions play also an important role.The de novo drug design Leapfrog simulations provided a series of novel compounds with predicted improved inhibition effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Binding Sites
  • Computer Simulation
  • Fullerenes / chemistry*
  • Fullerenes / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Quantitative Structure-Activity Relationship

Substances

  • Amino Acids
  • Anti-HIV Agents
  • Fullerenes
  • Aspartic Acid Endopeptidases