An algorithmic search through all possible conformations to identify the minimum energy configuration (the native state) would take an immense duration; however in reality protein folding happens very quickly, even in the case of the most complex structures, suggesting that the transitions are somehow guided into a stable state through an uneven energy landscape.
The "paradox" is that most small proteins fold spontaneously on a millisecond or even microsecond time scale.
The solution to this paradox has been established by computational approaches to protein structure prediction.
[10] Levinthal's paradox was cited on the first page of the Scientific Background to the 2024 Nobel Prize in Chemistry (awarded to David Baker, Demis Hassabis, and John M. Jumper for computational protein design and protein structure prediction) by way of demonstrating the sheer scale of the problem given the astronomical number of permutations.
[11] According to Edward Trifonov and Igor Berezovsky, proteins fold by subunits (modules) of the size of 25–30 amino acids.