The structural characterization of a complex of α-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 α-bungarotoxin epitope mapping, was adopted. Two similar structures were obtained for the complex, both of them stabilized by cation-π 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.

Abbreviations used: α-bgt, α-bungarotoxin; CDR, complementarity determining region; nAchR, nicotinic acetylcholine receptor; PDB, Protein Data Bank; scFv, single chain antibody fragment.

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