Prediction of 5-HT3 receptor agonist-binding residues using homology modeling

Biophys J. 2003 Apr;84(4):2338-44. doi: 10.1016/S0006-3495(03)75039-5.


5-HT(3) receptors demonstrate significant structural and functional homology to other members of the Cys-loop ligand-gated ion channel superfamily. The extracellular domains of these receptors share similar sequence homology (approximately 20%) with Limnaea acetylcholine binding protein, for which an x-ray crystal structure is available. We used this structure as a template for computer-based homology modeling of the 5-HT(3) receptor extracellular domain. AutoDock software was used to dock 5-HT into the putative 5-HT(3) receptor ligand-binding site, resulting in seven alternative energetically favorable models. Residues located no more than 5 A from the docked 5-HT were identified for each model; of these, 12 were found to be common to all seven models with five others present in only certain models. Some docking models reflected the cation-pi interaction previously demonstrated for W183, and data from these and other studies were used to define our preferred models.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Computer Simulation
  • Extracellular Fluid / chemistry
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Subunits
  • Receptors, Serotonin, 5-HT3 / chemistry*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Sequence Homology
  • Serotonin Receptor Agonists / chemistry


  • AChBP protein, Lymnaea
  • Carrier Proteins
  • Protein Subunits
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists