title: Levinthal's question revisited, and answered.
abstract: Attempts to answer the Levinthal question "How proteins fold to give such a unique structure" are discussed. In the first part of this article, we focus on a few reasons as to why the solution to the protein-folding problem (PFP) has been elusive for a very long time. One is a result of the misinterpretation of Anfinsen's Thermodynamic hypothesis which led to the conclusion that the native structure of a protein must be at a global minimum of the Gibbs energy. The second is the result of the adherence to the hydrophobic paradigm, and at the same time ignoring a whole repertoire of hydrophilic effects. It is argued that switching from a target-based to a caused-based approach, and adopting the hydrophilic paradigm leads straightforwardly to a simple answer to Levinthal's question, as well as to a solution of the PFP.
authors.affiliation: Department of Physical Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel. arieh@fh.huji.ac.il
authors.forename: Arieh
authors.initials: A
authors.lastname: Ben-Naim
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D011506:Proteins