Open AccessIntermediates can accelerate protein folding
Author(s) -
Clemens Wagner,
Thomas Kiefhaber
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.12.6716
Subject(s) - limiting , protein folding , folding (dsp implementation) , chemical physics , chemistry , folding funnel , activation barrier , maxima and minima , downhill folding , transition state , crystallography , computational chemistry , phi value analysis , biochemistry , density functional theory , catalysis , mechanical engineering , mathematical analysis , electrical engineering , mathematics , engineering
The effect of intermediates on the rate of protein folding is explored by applying Kramers’ theory of diffusive barrier crossing in the high friction limit. Intermediates are represented as local minima in the transition barrier. We observe that very large or very small additional barriers created by the intermediates slow down the folding process. The rate of folding markedly increases, however, when the additional barriers become >1kB Tbut leave the overall barrier height unchanged. This rate-enhancing effect is caused by a favorable entropic contribution to the free energy of activation, and it increases with the number of intermediates up to a limiting value. From these calculations, we conclude that optimized transition barriers should contain partially folded high energy intermediates.