In the first part of this talk I will discuss the need for a paradigm shift from hydrophobic ((HφO) ) to a hydrophilic ( HφI) based theory of protein folding. Next, I will discuss the various types of solvent-induced forces that are exerted on various groups on the protein. It is argued, both theoretically and by simulations that the HφI - HφI solvent-induced forces are likely to be the strongest. Therefore, it is suggesred that these forces are also the forces that force the protein to fold, in a short time, along a narrow range of pathways. This paradigm shift also answers Levinthal's question about the factors that "speed" and "guide" the folding of proteins.

References

C. Levinthal (1969). How to Fold Graciously. Mössbauer Spectroscopy in Biological Systems Proceedings, Vol. 67, No. 41, 1969, pp. 22-26

A. Ben-Naim (2012). Levinthal’s Question Revisited, and Answered. Journal of Biomolecular Structure and Dynamics 30, 113-124. doi.10.1080/07391102.2012.674286

A. Ben-Naim (2013). The Protein Folding Problem and its Solutions. World Scientific, Singapore.

A. Ben-Naim (2011). Molecular Theory of Water and Aqueous Solutions; Part II: The Role of Water in Protein folding Self assembly and Molecular Recognition. World Scientific, Singapore.