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Epitope specificity of two anti‐morphine monoclonal antibodies: In vitro and in silico studies
Author(s) -
Trofimov Alexander V.,
Sokolov Alexey V.,
Rak Alexandra Y.,
Ischenko Alexander M.,
Kudling Tatiana V.,
Vakhrushev Andrey V.,
Gorbunov Alexei A.
Publication year - 2020
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2845
Subject(s) - monoclonal antibody , hapten , epitope , antibody , morphine , chemistry , docking (animal) , in silico , antigen , immunoassay , surface plasmon resonance , in vitro , microbiology and biotechnology , computational biology , pharmacology , biochemistry , biology , immunology , medicine , materials science , nursing , gene , nanoparticle , nanotechnology
Monoclonal antibodies (mAbs) against morphine are important in the development of immunotherapeutic and diagnostic methods for the treatment and prevention of drug addiction. By the surface plasmon resonance (SPR) and enzyme immunoassay techniques, we characterized two previously obtained mAbs 3K11 and 6G1 and showed their ability to recognize free morphine and morphine‐containing antigens in different ways because of the epitope specificity thereof. Using the defined amino acid sequences, we obtained three‐dimensional models of the variable regions of Fab fragments of these antibodies and compared them with the known sequence and spatial structure of the anti‐morphine antibody 9B1. Docking simulations are performed to obtain models of the antibodies complexes with morphine. Differences in the models of 3K11 and 6G1 complexes with morphine correlate with their experimentally detected epitope specificity. The results, in particular, can be used for the structure‐based design of the corresponding humanized antibodies. According to our modeling and docking results, the very different modes of morphine binding to mAbs 3K11 and 6G1 are qualitatively similar to those previously reported for cocaine and two anti‐cocaine antibodies. Thus, the obtained structural information brings more insight into the hapten recognition diversity.