Application of a novel in silico high-throughput screen to identify selective inhibitors for protein-protein interactions

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5411-3. doi: 10.1016/j.bmcl.2010.07.103. Epub 2010 Jul 30.

Abstract

Increasing numbers of target protein structures available for computational studies makes the structure-based screening paradigm more attractive for initial hit indentification. We have developed a novel in silico screening methodology incorporating Molecular Mechanics (MM)/implicit solvent methods to evaluate binding free energies and applied this technology to the identification of inhibitors of the TLR4/MD-2 interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Drug Design*
  • High-Throughput Screening Assays / methods*
  • Humans
  • Lipopolysaccharides / immunology
  • Lymphocyte Antigen 96 / antagonists & inhibitors*
  • Lymphocyte Antigen 96 / chemistry
  • Lymphocyte Antigen 96 / metabolism*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Models, Molecular
  • Protein Binding / drug effects
  • Protein Interaction Mapping / methods*
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / chemistry
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Toll-Like Receptor 4