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Protein folding problem: enigma, paradox, solutionстатья
- Авторы: Finkelstein Alexei V., Bogatyreva Natalya S., Ivankov Dmitry N., Garbuzynskiy Sergiy O.
- Журнал: Biophysical Reviews
- Том: 14
- Номер: 6
- Год издания: 2022
- Издательство: Springer Verlag
- Местоположение издательства: Germany
- Первая страница: 1255
- Последняя страница: 1272
- DOI: 10.1007/s12551-022-01000-1
- Аннотация: The ability of protein chains to spontaneously form their three-dimensional structures is a long-standing mystery in molecularbiology. The most conceptual aspect of this mystery is how the protein chain can fnd its native, “working” spatial structure(which, for not too big protein chains, corresponds to the global free energy minimum) in a biologically reasonable time,without exhaustive enumeration of all possible conformations, which would take billions of years. This is the so-called“Levinthal’s paradox.” In this review, we discuss the key ideas and discoveries leading to the current understanding of protein folding kinetics, including folding landscapes and funnels, free energy barriers at the folding/unfolding pathways, andthe solution of Levinthal’s paradox. A special role here is played by the “all-or-none” phase transition occurring at proteinfolding and unfolding and by the point of thermodynamic (and kinetic) equilibrium between the “native” and the “unfolded”phases of the protein chain (where the theory obtains the simplest form). The modern theory provides an understanding ofkey features of protein folding and, in good agreement with experiments, it (i) outlines the chain length-dependent range ofprotein folding times, (ii) predicts the observed maximal size of “foldable” proteins and domains. Besides, it predicts themaximal size of proteins and domains that fold under solely thermodynamic (rather than kinetic) control. Complementarily,a theoretical analysis of the number of possible protein folding patterns, performed at the level of formation and assemblyof secondary structures, correctly outlines the upper limit of protein folding times.
- Добавил в систему: Финкельштейн Алексей Витальевич