Folding funnel

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A folding funnel

The folding funnel (more precisely, protein folding funnel , English folding funnel ) is a postulated curve in a funnel-like energy diagram of protein folding .

properties

According to the Anfinsen dogma , the native and folded conformation of a protein is at the same time the most favorable in terms of energy, which is why the protein folding under cellular conditions in most cases develops independently (without chaperones ). The native form has a local minimum in the free energy between different possible folds. The folding funnel is a model for describing the thermodynamics of protein folding. With the help of this model one could avoid the Levinthal paradox , in which it was stated that starting from the initial conformation of a protein one “tried” every possible conformation in order to reach its native state, which would take about 10 24 years to complete. With the folding funnel you can clearly explain that, for example, a ball reaches the center of the funnel at every position on the funnel edge. This would also be the case with the folding process of a protein, namely that regardless of the initial conformation of the protein, it only has to follow the potential gradient in order to reach its energy minimum.

The wide opening of the funnel corresponds to all possible denatured conformations - the conformational entropy is highest at this point. When the free enthalpy decreases, the conformational possibilities also decrease. The local minima on the sides of the funnel represent the semi-stable intermediate stages that, depending on their depth, can facilitate or hinder the formation of the native structure. In the lower area is the native state with a precisely defined conformation.

history

The name was coined in 1992 by José Onuchic .

literature

  • Kerson Huang: Lectures on Statistical Physics and Protein Folding. World Scientific, 2005, ISBN 978-981-256-938-7 , p. 101.
  • David Sheehan: Physical Biochemistry: Principles and Applications. John Wiley & Sons, 2013, ISBN 978-1-118-68748-2 , p. 205.

Individual evidence

  1. Michael Groß: Got to the funnel - the new view of protein folding. In: Spectrum of Science. June 1997. Retrieved June 23, 2017 .
  2. Jeremy M. Berg, Lubert Stryer , John L. Tymoczko: Stryer Biochemistry . Springer-Verlag, 2014, p. 55 ( limited preview in Google Book search).
  3. ^ PE Leopold, M. Montal, JN Onuchic: Protein folding funnels: a kinetic approach to the sequence-structure relationship. In: Proceedings of the National Academy of Sciences . Volume 89, Number 18, September 1992, pp. 8721-8725, PMID 1528885 , PMC 49992 (free full text).