B1 Kirjoitus tieteellisessä aikakauslehdessä
Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2 (2021)
Artyushenko, P. V., Mironov, V. A., Morozov, D. I., Shchugoreva, I. A., Borbone, N., Tomilin, F. N., & Kichkailo, A. S. (2021). Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2. Sibirskoe Medicinskoe Obozrenie, 2021(2), 66-67. https://doi.org/10.20333/2500136-2021-2-66-67
JYU-tekijät tai -toimittajat
Julkaisun tiedot
Julkaisun kaikki tekijät tai toimittajat: Artyushenko, P. V.; Mironov, V. A.; Morozov, D. I.; Shchugoreva, I. A.; Borbone, N.; Tomilin, F. N.; Kichkailo, A. S.
Lehti tai sarja: Sibirskoe Medicinskoe Obozrenie
ISSN: 1819-9496
eISSN: 2500-0136
Julkaisuvuosi: 2021
Volyymi: 2021
Lehden numero: 2
Artikkelin sivunumerot: 66-67
Kustantaja: Krasnoyarsk State Medical University
Julkaisumaa: Venäjä
Julkaisun kieli: englanti
DOI: https://doi.org/10.20333/2500136-2021-2-66-67
Pysyvä verkko-osoite: https://smr.krasgmu.ru/journal/2089_10_artyushenko.pdf
Julkaisun avoin saatavuus: Avoimesti saatavilla
Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava
Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/78608
Lisätietoja: Conference materials. 5th International Seminar "Digital Medicines at the Junction of Sciences."
Tiivistelmä
Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied.
Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifications in order to increase the binding with the RBD. Thus, a new aptamer Apt25 was designed. The procedure of 1) aptamer structure modeling/modification, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed sev-eral times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. The calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods.
Conclusion. The proposed computational approach to selection and refinement of aptamers is universal and can be used for wide range of molecular ligands and targets.
YSO-asiasanat: koronavirukset; SARS-CoV-2-virus; reseptorit (biokemia); oligonukleotidit; molekyylidynamiikka; kvanttikemia; laskennallinen kemia
Vapaat asiasanat: aptamer; receptor-binding domain; SARS-CoV-2; selection
Liittyvät organisaatiot
OKM-raportointi: Kyllä
Raportointivuosi: 2021