How to fold graciously

By C. Levinthal. 1969

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

AlphaFold2 and its applications in the fields of biology and medicine (2023, background): “The possible conformational number of a protein with several hundred amino acids is estimated to be about 10(300).(34) Although great progresses have been made in conformational search algorithms, as well as computing power and storage space, de novo modeling is still only applicable to small protei”
TM-align: a protein structure alignment algorithm based on the TM-score (2005, neutral): “Since the accessible conformational space of a medium size protein is astronomical (35), while the number of folds of solved proteins in the PDB (or even the folds existing in nature) is limited, it is conceivable that the possibility of a misfolded structure being close to any native structures…”
Protein structure prediction from sequence variation (2012, background): “Clearly, and unfortunately, the de novo structure prediction problem does not scale 13 , the conformational search space increases exponentially as the size of the protein increases, presenting a fundamental computational challenge, even for fragment-based methods 14 .”
De novo protein design, a retrospective (2020, background): “possible backbone conformations for a protein of this size represents an astronomically large number (10(100)), indicating that folding cannot occur by a random search of conformational space (Levinthal, 1969; Bryngelson et al., 1995).”