Membrane and Cell BiologyMembrane and Cell BiologyБиологические мембраны0233-47553034-5219The Russian Academy of Sciences66742610.31857/S0233475524050093cbfpadОБЗОРЫResearch ArticleLipid-mediated adaptation of proteins and peptides in cell membranesЛипид-опосредованная адаптация белков и пептидов в клеточных мембранахPolyanskyA. A.ПолянскийА. А.
Russian Federation
r-efremov@yandex.ruEfremovR. G.ЕфремовР. Г.
Russian Federation
r-efremov@yandex.ruShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesИнститут биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАНNational Research University Higher School of EconomicsНациональный исследовательский университет Высшая школа экономикиMoscow Institute of Physics and Technology (State University)Московский физико-технический институт (Национальный исследовательский университет)04112024415-647349126022025Copyright ©; 2024, The Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024The Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0233-4755/article/view/667426

The paper overviews the results of computational studies of the molecular mechanisms underlying the adaptation of model cell membranes taking place during their interaction with proteins and peptides. We discuss changes in the structural and dynamic parameters of the water–lipid environment, the hydrophobic/hydrophilic organization of the lipid bilayer surface (the so-called “mosaicity”), etc. Taken together, these effects are called the “membrane response” (MR) and constitute the most important ability of the cell membranes to respond specifically and consistently to the incorporation of extraneous agents, primarily proteins and peptides, and their subsequent functioning. The results of the authors’ long-term research in the field of molecular modeling of MR processes with various spatial and temporal characteristics are described, from the effects of binding of individual lipid molecules to proteins to changes in the integral macroscopic parameters of membranes. The bulk of the results were obtained using the “dynamic molecular portrait” approach developed by the authors. The biological role of the observed phenomena and potential ways of rationally designing artificial membrane systems with specified MR characteristics are discussed. This, in turn, is important for targeted changes in the activity profile of proteins and peptides exerting action on biomembranes, not least as promising pharmacological agents.

Представлены результаты исследований в компьютерном эксперименте молекулярных механизмов адаптации модельных клеточных мембран, реализующейся в ходе их взаимодействия с белками и пептидами. Речь идет об изменении структурно-динамических параметров водно-липидной среды, гидрофобной/гидрофильной организации поверхности липидного бислоя (так называемой «мозаичности») и пр. Взятые в совокупности, эти эффекты получили название «мембранного ответа» (МО) – важнейшей способности клеточных мембран специфично и устойчиво реагировать на встраивание и функционирование в них внешних агентов, в первую очередь – белков и пептидов. Описаны полученные в ходе многолетних исследований результаты авторов в области молекулярного моделирования процессов МО с различными пространственно-временными характеристиками – от эффектов связывания с белками отдельных молекул липидов до изменения интегральных макроскопических параметров мембран. Основная часть результатов получена с использованием разработанной авторами технологии «динамического молекулярного портрета». Обсуждаются биологическая роль наблюдаемых явлений и возможные пути рационального проектирования искусственных мембранных систем с заданными характеристиками МО. Это, в свою очередь, важно для направленного изменения профиля активности белков и пептидов, действующих на биомембраны, в том числе в качестве перспективных фармакологических агентов.

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