Youtao Song, Yao Song, Xing Chen, School of Life Sciences

Abstract: To date, there have been many hypotheses on protein folding and certain progress surely has been made, such as Anfinsen’ s dogma (1), Levinthal paradox (2). Recently, Mittal et al. analyzed close to 4,000 folded proteins from their published crystal structures in the protein data bank (PDB) with a bioinformatics and computational method, and innovatively proposed that protein folding is a direct consequence of a narrow band of stoichiometric occurrences of amino-acids in primary sequences, regardless of the size and the fold of a protein (3). Contrary to all prevalent views, this hypothesis actually negated the roles of specific aminoacid interactions and the sequence order of the amino acids in protein folding. In this connection, it should be noted that preferential interactions between amino acids are the basis for introducing knowledge-based potentials, which in turn provide the underpinning for present day three-dimensional protein structure prediction by modeling and simulation (4-7 and references therein). Although their data analysis approaches seem scientifically correct, the “unified conclusion” drawn from a quantity of statistic data may not explain principles complied by every individual protein for its folding. Nevertheless, spatial distribution of neighborhoods for all amino-acids, rather than residues adjacent along the primary sequence, determine the protein folding, as proposed by Mittal et al. is a meaningful finding.

Read the article here:   136-The yeast prion case could there be a uniform concept underlying complex protein folding.pdf