A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs

J Mol Model. 2011 Aug;17(8):1847-54. doi: 10.1007/s00894-010-0890-6. Epub 2010 Nov 16.


Molecular docking is a reliable method with which to identify the binding conformations of substrates, inducers and inhibitors of cytochrome P450 (CYP) enzymes. We used the docking method to explore possible binding modes of an entry inhibitor (maraviroc) and non-nucleoside reverse transcriptase inhibitors (delavirdine, efavirenz and etravirine) to cytochrome P450 3A4 (CYP3A4). In addition, docking results were compared with the binding conformations of HIV protease drugs to infer the binding site residues and potential drug-drug interaction profiles for combination therapy in the treatment of AIDS. We observed that efavirenz and etravirine induce metabolism of co-administered drugs by binding to a unique position in the active site of CYP3A4. Dosage adjustment is required for delavirdine and maraviroc when combined with HIV protease drugs. The present results are in good agreement with experimental data from drug interaction profiles. The information provided in this paper will be helpful in furthering our understanding the functions of CYP3A4, and could aid in the design of new drugs that would be metabolized easily without having any drug-drug interaction profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / metabolism
  • Binding Sites
  • Catalytic Domain
  • Cytochrome P-450 CYP3A / chemistry*
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Design
  • Drug Interactions
  • Humans
  • Models, Molecular
  • Molecular Conformation


  • Anti-HIV Agents
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human