The loop hypothesis: contribution of early formed specific non-local interactions to the determination of protein folding pathways

Biophysics Reviews
Tomer OreviElisha Haas

Abstract

The extremely fast and efficient folding transition (in seconds) of globular proteins led to the search for some unifying principles embedded in the physics of the folding polypeptides. Most of the proposed mechanisms highlight the role of local interactions that stabilize secondary structure elements or a folding nucleus as the starting point of the folding pathways, i.e., a "bottom-up" mechanism. Non-local interactions were assumed either to stabilize the nucleus or lead to the later steps of coalescence of the secondary structure elements. An alternative mechanism was proposed, an "up-down" mechanism in which it was assumed that folding starts with the formation of very few non-local interactions which form closed long loops at the initiation of folding. The possible biological advantage of this mechanism, the "loop hypothesis", is that the hydrophobic collapse is associated with ordered compactization which reduces the chance for degradation and misfolding. In the present review the experiments, simulations and theoretical consideration that either directly or indirectly support this mechanism are summarized. It is argued that experiments monitoring the time-dependent development of the formation of specifically targeted ea...Continue Reading

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Citations

Oct 22, 2016·Progress in Biophysics and Molecular Biology·Igor N BerezovskyZejun Zheng
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin T WaltersS Walter Englander
Dec 10, 2019·Current Opinion in Structural Biology·Lavi S Bigman, Yaakov Levy
Jul 24, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Harshita Rastogi, Pramit K Chowdhury
Mar 23, 2019·The Journal of Physical Chemistry. B·Fernando Bergasa-CaceresHerschel A Rabitz

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