On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data

J Comput Aided Mol Des. 2003 Feb-Apr;17(2-4):129-34. doi: 10.1023/a:1025313705564.


There are several indications that a given compound or a set of related compounds can bind in different modes to a specific binding site of a protein. This is especially evident from X-ray crystallographic structures of ligand-protein complexes. The availability of multiple binding modes of a ligand in a binding site may present an advantage in drug design when simultaneously optimizing several criteria. In the case of the design of anti-HIV compounds we observed that the more active compounds that are also resilient against mutation of the non-nucleoside binding site of HIV1-reverse transcriptase make use of more binding modes than the less active and resilient compounds.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Binding Sites
  • Crystallization
  • Drug Design
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / metabolism
  • Ligands
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Structure
  • Protein Binding*
  • Protein Conformation
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / metabolism


  • Anti-HIV Agents
  • Ligands
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase