Рубрики:
BIOLOGICAL MACROMOLECULES
SOLUTION SCATTERING
BINDING
SPIKE
Кл.слова (ненормированные):
aptamers -- fragment molecular orbitals method -- molecular dynamics -- SARS-CoV-2 -- SAXS
BIOLOGICAL MACROMOLECULES
SOLUTION SCATTERING
BINDING
SPIKE
Кл.слова (ненормированные):
aptamers -- fragment molecular orbitals method -- molecular dynamics -- SARS-CoV-2 -- SAXS
Аннотация: Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity by using small-angle X-ray scattering, cytometry, and fluorescence polarization. By using a new iterative design procedure, structure- and interaction-based drug design (SIBDD), a highly specific aptamer to the receptor-binding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variants.
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Держатели документа:
Lomonosov Moscow State Univ, Dept Chem, Moscow 119991, Russia.
Kyungpook Natl Univ, Dept Chem, Daegu 702701, South Korea.
Fed Res Ctr KSC SB RAS, Lab Digital Controlled Drugs & Theranost, Krasnoyarsk 660036, Russia.
Natl Tsing Hua Univ, Dept Chem Engn, Hsinchu 30013, Taiwan.
Siberian Fed Univ, Sch Nonferrous Met & Mat Sci, Krasnoyarsk 660041, Russia.
IRCCS Neuromed Ist Neurol Mediterraneo Pozzilli, Via Atinense 18, I-86077 Pozzilli, Italy.
Krasnoyarsk State Med Univ, Lab Biomol & Med Technol, Krasnoyarsk 660022, Russia.
Univ Jyvaskyla, Nanosci Ctr, Jyvaskyla 40014, Finland.
Univ Jyvaskyla, Dept Chem, Jyvaskyla 40014, Finland.
Univ Naples Federico II, Dept Pharm, I-80138 Naples, Italy.
Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy.
Kirensky Inst Phys, Lab Phys Magnet Phenomena, Krasnoyarsk 660012, Russia.
Siberian Fed Univ, Sch Fundamental Biol & Biotechnol, Krasnoyarsk 660041, Russia.
Xiamen Univ, Coll Chem & Chem Engn, Dept Chem Biol, Xiamen 361005, Peoples R China.
State Res Ctr Virol & Biotechnol Vector, Koltsov 630559, Russia.
NRC Kurchatov Inst, Moscow 117259, Russia.
Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia.
Russian Acad Sci, Res Ctr Biotechnol, AN Bach Inst Biochem, Lab Immunobiochem, Moscow 119071, Russia.
Tomsk State Univ, Lab Adv Mat & Technol, Tomsk 634050, Russia.
Altai State Univ, Barnaul 656049, Russia.
Fed Res Ctr KSC SB RAS, Dept Mol Elect, Krasnoyarsk 660036, Russia.
Krasnoyarsk State Med Univ, Dept Infect Dis & Epidemiol, Krasnoyarsk 660022, Russia.
Natl Pingtung Univ, Dept Appl Chem, Pingtung 900391, Taiwan.
Natl Synchrotron Radiat Res Ctr, Hsinchu Sci Pk, Hsinchu 30076, Taiwan.
Res Natl Council CNR, Inst Genet & Biomed Res IRGB, I-09042 Milan, Italy.
Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med, Shanghai 200127, Peoples R China.
Natl Inst Adv Ind Sci & Technol, Res Ctr Computat Design Adv Funct Mat, Tsukuba, Ibaraki 3058560, Japan.
Hunan Univ, Coll Chem & Chem Engn, Changsha 410082, Hunan, Peoples R China.
Argonne Natl Lab, Computat Sci Div, Lemont, IL 60439 USA.
Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada.
Доп.точки доступа:
Mironov, Vladimir; Shchugoreva, I. A.; Artyushenko, P. V.; Артюшенко, Полина Владимировна; Morozov, D. I.; Морозов, Дмитрий И.; Borbone, N.; Oliviero, G.; Zamay, T. N.; Замай, Т. Н.; Moryachkov, R. V.; Морячков, Роман Владимирович; Kolovskaya, .; Коловская О. С.; Lukyanenko, K. A.; Лукьяненко Кирилл А.; Song, Y. L.; Merkuleva, I. A.; Zabluda, V. N.; Заблуда, Владимир Николаевич; Peters, G.; Koroleva, L. S.; Veprintsev, D. V.; Glazyrin, Y. E.; Volosnikova, E. A.; Belenkaya, S. V.; Esina, T. I.; Isaeva, A. A.; Nesmeyanova, .; Shanshin, D. V.; Berlina, A. N.; Komova, N. S.; Svetlichnyi, V. A.; Silnikov, V. N.; Shcherbakov, D. N.; Zamay, G. S.; Замай, Галина Сергеевна; Zamay, S. S.; Замай, С. С.; Smolyarova, T. E.; Смолярова, Татьяна Евгеньевна; Tikhonova, E. P.; Chen, U. S.; Jeng, G.; Condorelli, V.; Franciscis, G.; Groenhof, C. Y.; Yang, A. A.; Moskovsky, D. G.; Fedorov, F. N.; Tomilin, F. N.; Томилин, Феликс Николаевич; Tan, Y.; Alexeev, M. V.; Berezovski, A. S.; Kichkailo, A.S.; Aptamerlab LCC; U.S. Department of Energy, Office of ScienceUnited States Department of Energy (DOE) [DE-AC02-06CH11357]; European UnionEuropean Commission [H2020-INFRAEDI-02-2018-823830, H2020-EINFRA-2015-1-675728, 872391, PRISAR2 872860]; CSC-IT center in Espoo, Finland; PRACE; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [19-03-00043]; Ministry of Science and Higher Education of Russian Federation (state assignment of the Research Center of Biotechnology RAS); Italian Ministry of Education and ResearchMinistry of Education, Universities and Research (MIUR) [FISR2020 _00177]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [OV1-170353]; Russian Science FoundationRussian Science Foundation (RSF) [21-73-20240]