Технологии поиска и исследования потенциально осциллирующих ферментативных систем

Многие процессы в живых организмах подвержены периодическим колебаниям на различных иерархических уровнях их организации: от молекулярного-генетического до популяционного и экологического. Осциллирующие процессы отвечают за клеточные циклы как у прокариот, так и у эукариот, за циркадные ритмы, синхронную связь дыхания с сердечными сокращениями и др. Колебания численностей организмов в природных популяциях могут быть обусловлены собственными свойствами популяций, их возрастной структурой, а также экологическими взаимоотношениями с другими видами. Наряду с экспериментальными подходами, для исследования осциллирующих биологических систем широко применяется математическое и компьютерное моделирование. В данной статье представлены классические математические модели, которые описывают осциллирующее поведение в биологических системах. Приведены методы поиска осциллирующих молекулярно-генетических систем на примере их частного случая – осциллирующих ферментативных систем. Рассмотрены факторы, влияющие на циклическую динамику в живых системах, характерные не только для молекулярно-генетического уровня, но и для более высоких уровней организации. Обсуждается применение различных способов описания генных сетей для моделирования осциллирующих молекулярно-генетических систем, где важнейшим фактором возникновения циклического поведения является наличие обратных связей. Представлены технологии поиска потенциально осциллирующих ферментативных систем. С помощью метода, описанного в статье, проводится поэтапный процесс построения и анализа сначала структурных моделей (графов) генных сетей, а затем реконструкции математических моделей и вычислительных экспериментов с ними. Структурные модели идеально подходят для задач автоматического поиска потенциальных осциллирующих контуров (связных подграфов), структура которых может соответствовать математической модели молекулярно-генетической системы, демонстрирующей осциллирующее поведение в динамике. При этом именно численное исследование математических моделей для отобранных контуров позволяет подтвердить наличие в них устойчивых предельных циклов. В качестве примера применения технологии проанализирована сеть из 300 метаболических реакций бактерии Escherichia coli с использованием инструментов математического и компьютерного моделирования. В частности, показано осциллирующее поведение для контура, реакции которого входят в путь биосинтеза триптофана.

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