Predicting the binding mode of known NCp7 inhibitors to facilitate the design of novel modulators

J Chem Inf Model. 2011 Feb 28;51(2):446-54. doi: 10.1021/ci100393m. Epub 2010 Dec 20.

Abstract

The HIV-1 nucleocapsid protein (NCp7) is an emerging target for antiretroviral therapy. Five hits have been reported to inhibit the NCp7-viral nucleic acids interaction at micromolar concentrations. We used two computationally refined structures of NCp7 as receptors to propose a reliable binding pose for these compounds, by means of computational methods. Theoretical binding modes are in agreement with available experimental data. Results lay the foundations for a rationale development of more effective NCp7 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Computational Biology / methods*
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Ligands
  • Molecular Dynamics Simulation
  • Protein Conformation
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reproducibility of Results
  • Structure-Activity Relationship
  • Thermodynamics
  • User-Computer Interface
  • gag Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*
  • gag Gene Products, Human Immunodeficiency Virus / chemistry
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • DNA, Viral
  • Ligands
  • NCP7 protein, Human immunodeficiency virus 1
  • RNA, Viral
  • gag Gene Products, Human Immunodeficiency Virus