The unsolved “solved-problem” of protein folding

Abstract

The problem of protein folding presents a puzzle of such intrigue and depth that the scientific community cannot even agree on a single statement of the problem ((Ben-Naim, 2012) and references therein). The interplay between notions like hydrophobicity as the driving force or folding and what sort of free energy concepts and coordinates are required shows more intrigue than one normally finds in “solved problems”. A central figure whose hypothesis has defined a great body of interpretations and misinterpretations of the problem is that of Anfinsen (1973). The first issue that Prof. Ben-Naim takes on in his recent article (Ben-Naim, 2012) entitled “Levinthal’s question revisited, and answered” is the idea that Anfinsen’s thermodynamic hypothesis of protein folding has been misinterpreted, often, leading in part to interpretations of Levinthal’s paradox (Levinthal, 1968).