title: The Levinthal paradox of the interactome.
abstract: The central biological question of the 21st century is: how does a viable cell emerge from the bewildering combinatorial complexity of its molecular components? Here, we estimate the combinatorics of self-assembling the protein constituents of a yeast cell, a number so vast that the functional interactome could only have emerged by iterative hierarchic assembly of its component sub-assemblies. A protein can undergo both reversible denaturation and hierarchic self-assembly spontaneously, but a functioning interactome must expend energy to achieve viability. Consequently, it is implausible that a completely "denatured" cell could be reversibly renatured spontaneously, like a protein. Instead, new cells are generated by the division of pre-existing cells, an unbroken chain of renewal tracking back through contingent conditions and evolving responses to the origin of life on the prebiotic earth. We surmise that this non-deterministic temporal continuum could not be reconstructed de novo under present conditions.
authors: VIB Department of Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium. ptompa@vub.ac.be
authors: Peter
authors: P
authors: Tompa
authors: George D
authors: GD
authors: Rose
mesh_terms: D005656:Fungal Proteins / Q000378:metabolism*; D008954:Models, Biological; D015233:Models, Statistical; D017510:Protein Folding; D025941:Protein Interaction Mapping; D020543:Proteome / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D020543:Proteome