Evolution of catalytic centers of antibodies by virtual screening of broad repertoire of mutants using supercomputer.

Autor: Golovin AV; Moscow State University, Moscow, 119991, Russia., Smirnov IV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia., Stepanova AV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia., Zalevskiy AO; Moscow State University, Moscow, 119991, Russia., Zlobin AS; Moscow State University, Moscow, 119991, Russia., Ponomarenko NA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia., Belogurov AA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia., Knorre VD; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia. vera.knorre@gmail.com., Hurs EN; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia., Chatziefthimiou SD; Hamburg Unit, European Molecular Biology Laboratory, Hamburg, Germany., Wilmanns M; Hamburg Unit, European Molecular Biology Laboratory, Hamburg, Germany., Blackburn GM; Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, UK., Khomutov RM; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia., Gabibov AG; Moscow State University, Moscow, 119991, Russia.; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Jazyk: angličtina
Zdroj: Doklady. Biochemistry and biophysics [Dokl Biochem Biophys] 2017 Jul; Vol. 475 (1), pp. 245-249. Date of Electronic Publication: 2017 Sep 02.
DOI: 10.1134/S1607672917040019
Abstrakt: 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.
Databáze: MEDLINE