Editing Protein folding (section)

=== Levinthal's paradox ===
In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. An estimate of 3<sup>300</sup> or 10<sup>143</sup> was made in one of his papers.<ref>{{Cite web|url=https://en.wikibooks.org/wiki/Structural_Biochemistry/Proteins/Protein_Folding#The_Levinthal_Paradox|title=Structural Biochemistry/Proteins/Protein Folding - Wikibooks, open books for an open world|website=en.wikibooks.org|access-date=2016-11-05}}</ref> [[Levinthal's paradox]] is a thought experiment based on the observation that if a protein were folded by sequential sampling of all possible conformations, it would take an astronomical amount of time to do so, even if the conformations were sampled at a rapid rate (on the [[nanosecond]] or [[picosecond]] scale).<ref>{{cite journal | last = Levinthal | first = Cyrus | name-list-style = vanc | year = 1968 | title = Are there pathways for protein folding? | url = http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.pdf | journal = Journal de Chimie Physique et de Physico-Chimie Biologique | volume = 65 | pages = 44–45 | archive-url = https://web.archive.org/web/20090902211239/http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.pdf | archive-date = 2009-09-02 | doi = 10.1051/jcp/1968650044 | bibcode = 1968JCP....65...44L }}</ref> Based upon the observation that proteins fold much faster than this, Levinthal then proposed that a random conformational search does not occur, and the protein must, therefore, fold through a series of meta-stable [[Reaction intermediate|intermediate states]].