1. Evolution of catalytic centers of antibodies by virtual screening of broad repertoire of mutants using supercomputer
- Author
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Alexey A. Belogurov, Spyros D. Chatziefthimiou, E. N. Hurs, R. M. Khomutov, Alexander Zlobin, Ivan V. Smirnov, Alexander G. Gabibov, G.M. Blackburn, V. D. Knorre, Matthias Wilmanns, Natalia A. Ponomarenko, A. V. Stepanova, A. O. Zalevskiy, and Andrey V. Golovin
- Subjects
Models, Molecular ,0301 basic medicine ,Protein Conformation ,Mutant ,Biophysics ,Nanotechnology ,Computational biology ,01 natural sciences ,Biochemistry ,Antibodies ,Catalysis ,03 medical and health sciences ,0103 physical sciences ,medicine ,Virtual screening ,010304 chemical physics ,biology ,Paraoxon ,Chemistry ,Computational Biology ,General Chemistry ,General Medicine ,equipment and supplies ,Supercomputer ,030104 developmental biology ,Mutation ,Biocatalysis ,biology.protein ,Antibody ,medicine.drug - Abstract
It is proposed to perform quantum mechanical/molecular dynamics calculations of chemical reactions that are planned to be catalyzed by antibodies and then conduct a virtual screening of the library of potential antibody mutants to select an optimal biocatalyst. We tested the effectiveness of this approach by the example of hydrolysis of organophosphorus toxicant paraoxon using kinetic approaches and X-ray analysis of the antibody biocatalyst designed de novo.
- Published
- 2017