The Levinthal paradox of the interactome.

TitleThe Levinthal paradox of the interactome.
Publication TypeJournal Article
Year of Publication2011
AuthorsTompa, P., and G. D. Rose
JournalProtein Sci
Volume20
Issue12
Pagination2074-9
Date Published2011 Dec
ISSN1469-896X
KeywordsFungal Proteins, Models, Biological, Models, Statistical, Protein Folding, Protein Interaction Mapping, Proteome, Yeasts
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.

DOI10.1002/pro.747
Alternate JournalProtein Sci.
PubMed ID21987416
PubMed Central IDPMC3302650