vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-417Research ArticleМолекулярная биологияMolecular biologyМОЛЕКУЛЯРНОЕ МОДЕЛИРОВАНИЕ ВЗАИМОДЕЙСТВИЙ АДЖИТОКСИНА 2 С ПОТЕНЦИАЛ-УПРАВЛЯЕМЫМ КАЛИЕВЫМ КАНАЛОМ Kv1.3MOLECULAR MODELING OF INTERACTIONS OF AGITOXIN 2 WITH VOLTAGE-GATED POTASSIUM CHANNEL Kv1.3ВолынцеваА. Д.VolyntsevaA. D.

мл. науч. сотр. кафедры биоинженерии биологического факультета,

119234, г. Москва, Ленинские горы, д. 1, стр. 12

Department of Bioengineering, School of Biology,

Leninskiye gory 1-12, Moscow, 119234

alenkavolynceva@gmail.comНовоселецкийВ. Н.NovoseletskyV. N.

канд. физ-мат. наук, доцент кафедры биоинженерии биологического факультета,

119234, г. Москва, Ленинские горы, д. 1, стр. 12

Department of Bioengineering, School of Biology,

Leninskiye gory 1-12, Moscow, 119234

valeryns@gmail.comШайтанК. В.ShaitanK. V.

докт. физ-мат. наук, профессор, зам. зав. кафедры биоинженерии биологического факультета,

119234, г. Москва, Ленинские горы, д. 1, стр. 12

Department of Bioengineering, School of Biology,

Leninskiye gory 1-12, Moscow, 119234

shaytan49@yandex.ruФеофановА. В.FeofanovA. V.

докт. биол. наук, профессор кафедры биоинженерии биологического факультета,

119234, г. Москва, Ленинские горы, д. 1, стр. 12

Department of Bioengineering, School of Biology,

Leninskiye gory 1-12, Moscow, 119234

avfeofanov@yandex.ruМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation2017220120177212934Copyright © Волынцева А.Д., Новоселецкий В.Н., Шайтан К.В., Феофанов А.В., 20172017Волынцева А.Д., Новоселецкий В.Н., Шайтан К.В., Феофанов А.В.Volyntseva A.D., Novoseletsky V.N., Shaitan K.V., Feofanov A.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/417

Потенциал-управляемый калиевый канал Kv1.3 участвует во многих процессах возбудимых и невозбудимых клеток: поддержании потенциала покоя, переносе сигнала, апоптозе, регуляции клеточного объёма, активации и пролиферации лейкоцитов. Блокирование этого канала является эффективным подходом для лечения аутоиммунных, онкологических, хронических воспалительных и метаболических заболеваний. Одними из наиболее перспективных блокаторов канала Kv1.3 являются токсины, выделенные из яда скорпионов. Знание молекулярных аспектов процесса связывания пептидных блокаторов с каналом является важным условием для создания высокоэффективных и селективных лигандов. В работе с помощью моделирования по гомологии и применения молекулярной динамики были построены комплексы гибридного канала KcsA-Kv1.3 с аджитоксином 2. Анализ образуемых контактов позволил выявить полную картину взаимодействий, а также идентифицировать ключевые остатки, ответственные за аффинность связывания токсина. Результаты вычислительного эксперимента согласуются с экспериментальными данными и могут быть важны для разработки лекарств.

Voltage-gated potassium channel Kv1.3 is involved in a number of processes in excitable and non-excitable cells: maintenance of resting membrane potential, transfer of signals, apoptosis, regulation of cell volume, activation and proliferation of white blood cells. Blocking this channel is an effective approach for the treatment of autoimmune, oncological, chronic inflammatory and metabolic diseases. The most prospective blockers of Kv1.3 are toxins isolated from the venom of scorpions. Knowledge of the molecular aspects of binding of peptide blockers with channel is an important condition for the creation of highly effective and selective ligands. In the present work a complex of hybrid channel KcsA-Kv1.3 with agitoxin 2 was built using homology modeling and molecular dynamics simulation. Analysis of formed contacts allowed us to reveal a complete pattern of interactions and to identify key residues that are responsible for the toxin binding affinity. Results of computational experiment are consistent with the experimental data and important for drug development.

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The authors declare that there are no conflicts of interest present.