Компьютерное конструирование трехмерной структуры цитохрома Р450 1А2 и поиск его потенциальных лигандов

ОСНОВНЫЕ ВЫВОДЫ РАБОТЫ.

1. Построена компьютерная модель трехмерной структуры цитохрома Р450 1А2 человека, достоверность которой подтверждается возможностью правильно предсказать региоспецифичность окисления известных субстратов этого фермента.

2. На основе прогнозирования пространственной структуры комплексов CYP1A2 с низкомолекулярными органическими соединениями разработаны два независимых уравнения для вычисления констант диссоциации таких комплексов (основанных на применении нейронных сетей и метода 3D-QSAR/CoMSIA). Оба этих подхода дают сходные результаты как для известных лигандов CYP1A2, так и для большого числа других соединений.

3. Использованные методы предсказания строения и свойств комплексов CYP1A2 позволили выявить 52 потенциальных лиганда этого фермента среди низкомолекулярных соединений, структуры которых приведены в ряде известных компьютерных банков данных (ASINEX, CMC, MayBridge).

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