Biochemical filtering of a protein-protein docking simulation identifies the structure of a complex between a recombinant antibody fragment and alpha-bungarotoxin

Biochem J. 2003 Apr 15;371(Pt 2):423-7. doi: 10.1042/BJ20021369.

Abstract

The structural characterization of a complex of alpha-bungarotoxin with a recombinant antibody fragment that mimics the acetylcholine receptor was achieved using docking simulation procedures. To drive the computer simulation towards a limited set of solutions with biological significance, a filter, incorporating general considerations of antigen-antibody interactions, specificity of the selected antibody fragment and results from alpha-bungarotoxin epitope mapping, was adopted. Two similar structures were obtained for the complex, both of them stabilized by cation-pi and hydrophobic interactions due to tyrosilyl residues of the antibody fragment. Site-directed mutagenesis studies, removing each of the latter aromatic residues and causing full inactivation of the interaction process between the antibody fragment and the neurotoxin, support the validity of the calculated structure of the complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Bungarotoxins / chemistry
  • Bungarotoxins / metabolism*
  • Computer Simulation
  • DNA Primers
  • Immunoglobulin Fragments / chemistry*
  • Immunoglobulin Fragments / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / metabolism*

Substances

  • Bungarotoxins
  • DNA Primers
  • Immunoglobulin Fragments
  • Proteins