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The role of SAXS and molecular simulations in 3D structure elucidation of a DNA aptamer against lung cancerстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 29 сентября 2021 г.
- Авторы: 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.
- Журнал: Molecular therapy. Nucleic acids
- Том: 25
- Год издания: 2021
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 316
- Последняя страница: 327
- DOI: 10.1016/j.omtn.2021.07.015
- Аннотация: 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 structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here, we present a general optimization procedure for finding the most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated LC-18 (LC-18t) aptamer LC-18t was developed. A three-dimensional (3D) shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes.
- Добавил в систему: Миронов Владимир Андреевич