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Биологи научились создавать идеальные белки

Дата: 08.11.2012, Просмотров: 6580, Комментариев: 56

Ученые из Университета Вашингтона в Сиетле разработали алгоритм, при помощи которого можно создавать белки с любой наперед заданной трехмерной структурой. Работа ученых опубликована в журнале Nature, там же можно прочитать ее краткое содержание.


Созданная биологами программа фактически позволяет предсказать, какую последовательность аминокислот должен иметь белок, чтобы при сворачивании он принял наперед заданную трехмерную конформацию. Работает алгоритм на основе анализа множества уже известных трехмерных структур и применения набора эмпирических правил.


В качестве теста метода авторы решили создать пять белков, которые не только не встречаются в природе, но и общий вид которых ("фолд", определяющий их структурное суперсемейство) отличается от известных образцов. После установления алгоритмом аминокислотных последовательностей-кандидатов, лучшие из них отбирали при помощи распределенных вычислений с привлечением волонтеров.


Затем искусственные белки синтезировали в бактериях, выделяли, очищали и отправляли на определение структуры методом ядерно-магнитного резонанса (ЯМР). При этом те ученые, которым было поручено экспериментально установить структуру, ничего не знали о расчетной структуре.


Оказалось, что расчетные и экспериментально установленные трехмерные структуры практически не отличаются друг от друга во всех пяти случаях.


Созданные таким образом белки авторы называют идеальными в том смысле, что их последовательность сформирована не эволюцией, а структурным расчетом. Если последовательность натуральных белков определяется их функцией и во многом случайна, то у идеальных белков она зависит только от структуры. Интересно, что такой взгляд подтверждает и температура денатурации полученных белков. Она достигает 100 градусов, что гораздо больше чем у "обычных" протеинов (около 40-50 градусов, хотя бывают и исключения).


Одна из самых важных и сложных задач современной биологии - определение трехмерной структуры белков по их аминокислотной последовательности. Сейчас она может быть решена очень неточно и только в некоторых очень ограниченных случаях. Обратная задача, с которой имели дело авторы, также представляет большие трудности. До этого полностью искусственную полипептидную трехмерную структуру удалось создать лишь однажды - в случае белка Top7.

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