This paradox is called the Levinthal paradox, after Cyrus Levinthal. Assuming that it would take 10 -13 s to change each conformation, the time required to "test" all conformations would be 5 x 10 34 s or 10 27 years, longer than the age of the universe (14 x 10 9 yr). If each amino acid can adopt only 3 possible conformations, the total number of conformations could be 3 100 = 5 x 10 47. Consider this greatly simplified view of protein folding for a protein containing 100 amino acids. ![]() In either case, given the number of possibly nonnative states, it is amazing that proteins fold to the native state at all, let alone in a reasonable time frame. Folding in vivo is often assisted by other proteins called folding chaperones. It also occurs when a fully-folded protein misfolds (such as during fevers in disease states) and has been prevented from folding by association with other molecules. Folding in vivo occurs as a protein is being made on a ribosome. In vitro folding is done in very defined conditions, typically using low concentrations of small proteins to minimize misfolding opportunities. ![]() We will discuss protein folding done in the lab (in vitro) as well as protein folding in the cell (in vivo). Creative Commons Attribution 4.0 International License. \): Protein Folding and Misfolding Landscape Eric H.-L.
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