Solution of Levinthal’s paradox is possible at the level of the formation and assembly of protein secondary structures

Abstract

The complete volume of a protein’s conformation space is smaller by many orders of magnitude at the level of secondary-structure elements as compared with the conformation of amino-acid residues. According to Levinthal’s estimate, the latter is ~10^2L, with L being the number of residues in the chain, while the former, at the level of secondary structures, increases no faster than ~L^N with N being the number of the secondary-structure elements. N is approximately L/15 according to the statistics of protein structures. This drastic decrease in the exponent (L/15 instead of 2L) considerably reduces the sampling space and explains the reason that sampling of the conformation space at the level of secondary-structure elements does not prevent the protein chain from finding its most stable structure.