HIV-RT Inhibitors

image023Description: HIV-1 reverse transcriptase (RT) is an important target for drugs used in the treatment of AIDS. Drugs known as non-nucleoside RT inhibitors (NNRTI) appear to alter the structural and dynamical properties of RT which in turn inhibit RTs ability to transcribe. Molecular dynamics, principal component analysis and binding free energy simulations are employed to explore the dynamics of RT and its interaction with a bound NNRTI, for both wild type and mutant RT. We show that a bound NNRTI hinders the motion of RT subdomains. Mutations in the non-nucleoside RT inhibitor binding pocket partially restore RT flexibility.

Goals: The goal of this project is to understand the impact of protein dynamics plays in the activity of this enzyme. In addition we are trying to elucidate the mutations play in drug resistance by potentially restoring the required dynamical motion of the enzyme.


  • Zhou, Z. et al. Docking of Non-nucleoside Inhibitors: Neotripterifordin and its Derivatives to HIV-1 Reverse Transcriptase, Proteins: Structure, Function, and Genetics. 49(4), 529-542. 2002
  • Zhou, Z. and J.D. Madura Relative Free Energy of Binding and Binding Mode Calculations of HIV-1 RT Inhibitors Based on Dock-MM-PB/GS. In press, Proteins, 2004.
  • Zhou, Z., and J.D. Madura, 3D-QSAR CoMFA and Docking Study on HIV-1 RT Non-nuclesodie inhibitors, TIBO derivatives. Submitted JCICS, 2004.
  • Zhou, Z., Madrid, M., Evanseck, J., Madura, J. Effect of a bound non-nucleoside RT inhibitor on the dynamics of HIV-1 Reverse Transcriptase, In preparation, Proteins, 2004.