Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2
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
Published inSibirskoe Medicinskoe Obozrenie
© ARTYUSHENKO P. V., MIRONOV V. A., MOROZOV D. I., SHCHUGOREVA I. A., BORBONE N., TOMILIN F. N., KICHKAILO A. S.
The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. 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. ...
PublisherKrasnoyarsk State Medical University
Publication in research information system
MetadataShow full item record
Showing items with similar title or keywords.
Mironov, Vladimir; Shchugoreva, Irina A.; Artyushenko, Polina V.; Morozov, Dmitry; Borbone, Nicola; Oliviero, Giorgia; Zamay, Tatiana N.; Moryachkov, Roman V.; Kolovskaya, Olga S.; Lukyanenko, Kirill A.; Song, Yangling; Merkuleva, Iuliia A.; Zabluda, Vladimir N.; Peters, Georgy; Koroleva, Lyudmila S.; Veprintsev, Dmitry V.; Glazyrin, Yury E.; Volosnikova, Ekaterina A.; Belenkaya, Svetlana V.; Esina, Tatiana I.; Isaeva, Anastasiya A.; Nesmeyanova, Valentina S.; Shanshin, Daniil V.; Berlina, Anna N.; Komova, Nadezhda S.; Svetlichnyi, Valery A.; Silnikov, Vladimir N.; Shcherbakov, Dmitriy N.; Zamay, Galina S.; Zamay, Sergey S.; Smolyarova, Tatyana; Tikhonova, Elena P.; Chen, Kelvin H.-C.; Jeng, U-Ser; Condorelli, Gerolama; de Franciscis, Vittorio; Groenhof, Gerrit; Yang, Chaoyong; Moskovsky, Alexander A.; Fedorov, Dmitri G.; Tomilin, Felix N.; Tan, Weihong; Alexeev, Yuri; Berezovski, Maxim V.; Kichkailo, Anna S. (Wiley-VCH Verlag, 2022)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 ...
Postila, Pekka (University of Jyväskylä, 2010)
Selection on two behavioral genes : fitness effects of receptor genes for arginine vasopressin 1a and oxytocin in the bank vole Myodes glareolus Lönn, Eija (University of Jyväskylä, 2017)Most variation in behavior is regulated by genes; nevertheless the mechanisms behind maintenance of genetic diversity at behavioral loci have remained mainly elusive in natural populations. I studied in my thesis ...
The Role of Small-Angle X-Ray Scattering and Molecular Simulations in 3D Structure Elucidation of a DNA Aptamer Against Lung Cancer Morozov, Dmitry; Mironov, Vladimir; Moryachkov, Roman V.; Shchugoreva, Irina A.; Artyushenko, Polina V.; Zamay, Galina S.; Kolovskaya, Olga S.; Zamay, Tatiana N.; Krat, Alexey V.; Molodenskiy, Dmitry S.; Zabluda, Vladimir N.; Veprintsev, Dmitry V.; Sokolov, Alexey E.; Zukov, Ruslan A.; Berezovski, Maxim V.; Tomilin, Felix N.; Fedorov, Dmitri G.; Alexeev, Yuri; Kichkailo, Anna S. (Elsevier, 2021)Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary ...
How to design and realize participation of stakeholders in MCDA processes? A framework for selecting an appropriate approach Marttunen, Mika; Mustajoki, Jyri; Dufva, Mikko; Karjalainen, Timo P. (2013)