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Investigation of the stereoselectivity of an anti‐amino acid antibody using molecular modeling and ligand docking
Author(s) -
Ranieri Daniel I.,
Corgliano Danielle M.,
Franco Elliott J.,
Hofstetter Heike,
Hofstetter Oliver
Publication year - 2008
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20522
Subject(s) - chemistry , stereochemistry , ligand (biochemistry) , docking (animal) , steric effects , enantiomer , tryptophan , binding site , molecular model , active site , amino acid , biochemistry , receptor , enzyme , medicine , nursing
The structure of the binding site of the stereoselective anti‐ D ‐amino acid antibody 67.36 was modeled utilizing web antibody modeling (WAM) and SWISS‐MODEL. Although docking experiments performed with an aromatic amino acid as model ligand were unsuccessful with the WAM structure, ligand binding was achieved with the SWISS‐MODEL structure. Incorporation of side‐chain flexibility within the binding site resulted in a protein structure that stereoselectively binds to the D ‐enantiomer of the model ligand. In addition to four hydrogen bonds that are formed between amino acid residues in the binding site and the ligand, a number of hydrophobic interactions are involved in the formation of the antibody‐ligand complex. The aromatic side chain of the ligand interacts with a tryptophan and a tyrosine residue in the binding site through π–π stacking. Fluorescence spectroscopic investigations also suggest the presence of tryptophan residues in the binding site, as ligand binding causes an enhancement of the antibody's intrinsic fluorescence at an emission wavelength of 350 nm. Based on the modeled antibody structure, the L ‐enantiomer of the model ligand cannot access the binding site due to steric hindrance. Additional docking experiments performed with D ‐phenylalanine and D ‐norvaline showed that these ligands are bound to the antibody in a way analogous to the D ‐enantiomer of the model ligand. Chirality, 2008. © 2008 Wiley‐Liss, Inc.