Levinthal's paradox

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/1992; 89(1):20-2. DOI: 10.1073/pnas.89.1.20
Source: PubMed


Levinthal's paradox is that finding the native folded state of a protein by a random search among all possible configurations can take an enormously long time. Yet proteins can fold in seconds or less. Mathematical analysis of a simple model shows that a small and physically reasonable energy bias against locally unfavorable configurations, of the order of a few kT, can reduce Levinthal's time to a biologically significant size.

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    • "Such a rapid rate of protein-folding would not be possible if protein-folding followed a simple stochastic process whereby the protein samples all possible conformations with equal probability. This concept, known as Levinthal's Paradox (Levinthal 1969; Zwanzig et al. 1992), thus suggests that the protein-folding follows a guided pathway of local interactions or kinetically controlled stable intermediate states. By the late 1960s, there was an increasing accumulation of experimental data detecting the presence of protein folding intermediates and partially folded transition states, primarily through non-simultaneous variation in spectroscopic properties upon protein unfolding (see, for example, Tanford et al. 1966). "
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    • "Here P(k, t) is the probability of occupation of state k at time t, and the growing and shrinking probabilities represent the transition rates between neighboring states. By using the fundamental relations [7] "
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    • "letter is fixed whenever it is typed correctly, then it would only take a few thousand keystrokes (Dawkins 1987; Zwanzig et al. 1992). There are only 4 letters in the RNA alphabet and the " words " are helixes and loops. "
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