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Open AccessReview

Solution of Levinthal’s Paradox and a Physical Theory of Protein Folding Times

1
Center of Life Sciences, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
2
Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia
3
Biology Department, Lomonosov Moscow State University, 119192 Moscow, Russia
4
Biotechnology Department, Lomonosov Moscow State University, 142290 Pushchino, Moscow Region, Russia
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 250; https://doi.org/10.3390/biom10020250
Received: 12 December 2019 / Revised: 30 January 2020 / Accepted: 1 February 2020 / Published: 6 February 2020
“How do proteins fold?” Researchers have been studying different aspects of this question for more than 50 years. The most conceptual aspect of the problem is how protein can find the global free energy minimum in a biologically reasonable time, without exhaustive enumeration of all possible conformations, the so-called “Levinthal’s paradox.” Less conceptual but still critical are aspects about factors defining folding times of particular proteins and about perspectives of machine learning for their prediction. We will discuss in this review the key ideas and discoveries leading to the current understanding of folding kinetics, including the solution of Levinthal’s paradox, as well as the current state of the art in the prediction of protein folding times.
Keywords: protein folding; Levinthal’s paradox; “all-or-none” transition; free energy barrier; folding funnel; detailed balance principle protein folding; Levinthal’s paradox; “all-or-none” transition; free energy barrier; folding funnel; detailed balance principle
MDPI and ACS Style

Ivankov, D.N.; Finkelstein, A.V. Solution of Levinthal’s Paradox and a Physical Theory of Protein Folding Times. Biomolecules 2020, 10, 250.

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