Сравнительный анализ белка NS5 штаммов трёх субтипов вируса клещевого энцефалита

Неструктурный белок 5 (NS5) вируса клещевого энцефалита является ферментом, который отвечает за копирование вирусной РНК и по трёхмерной структуре имеет сходство с РНК-полимеразами других вирусных семейств. Вирус клещевого энцефалита разделяется на три субтипа, различающиеся некоторыми из аминокислотных остатков в белках вируса, в том числе в белке NS5. Методы структурной биоинформатики позволяют реконструировать трёхмерную структуру белка NS5 для различных субтипов вируса.

В работе выполнен сравнительный анализ последовательностей белка NS5 для трёх субтипов вируса и были определены участки белка, в которых проявляется наибольшее различие между субтипами и внутри субтипов. «Зоны накопления мутаций», определённые таким образом, локализованы в домене метилтрансферазы, зоне междоменного интерефейса и трёх субдоменах домена полимеразы белка NS5. Обнаружена связь положения мутаций в белке NS5 с подвижностью участков белка в трёхмерной модели, определённых с помощью метода нормальных мод. А именно наиболее важные мутации локализованы в зонах, где наиболее велика амплитуда коллективных синхронных колебательных движений обоих доменов белка: во втором кармане связывания иона цинка в домене полимеразы, области N-концевого удлинения в междоменной зоне и области окружения активного центра домена метилтрансферазы.

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