How does a protein fold? View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1994-05

AUTHORS

Andrej S˘ali, Eugene Shakhnovich, Martin Karplus

ABSTRACT

THE number of all possible conformations of a polypeptide chain is too large to be sampled exhaustively. Nevertheless, protein sequences do fold into unique native states in seconds (the Levinthal paradox). To determine how the Levinthal paradox is resolved, we use a lattice Monte Carlo model in which the global minimum (native state) is known. The necessary and sufficient condition for folding in this model is that the native state be a pronounced global minimum on the potential surface. This guarantees thermodynamic stability of the native state at a temperature where the chain does not get trapped in local minima. Folding starts by a rapid collapse from a random-coil state to a random semi-compact globule. It then proceeds by a slow, rate-determining search through the semi-compact states to find a transition state from which the chain folds rapidly to the native state. The elements of the folding mechanism that lead to the resolution of the Levinthal paradox are the reduced number of conformations that need to be searched in the semi-compact globule (˜1010 versus ˜1016 for the random coil) and the existence of many (˜103) transition states. The results have evolutionary implications and suggest principles for the folding of real proteins. More... »

PAGES

248-251

References to SciGraph publications

  • 1976-04. Protein-folding dynamics in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/369248a0

    DOI

    http://dx.doi.org/10.1038/369248a0

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/7710478


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