Understanding the folding rates and folding nuclei of globular proteins

Alexei V. Finkelstein, Dmitry N. Ivankov, Sergiy O. Garbuzynskiy, Oxana V. Galzitskaya

Research output: Contribution to journalReview articlepeer-review

21 Citations (Scopus)

Abstract

The first part of this paper contains an overview of protein structures, their spontaneous formation ("folding"), and the thermodynamic and kinetic aspects of this phenomenon, as revealed by in vitro experiments. It is stressed that universal features of folding are observed near the point of thermodynamic equilibrium between the native and denatured states of the protein. Here the "two-state" ("denatured state" ↔ "native state") transition proceeds without accumulation of metastable intermediates, but includes only the unstable "transition state". This state, which is the most unstable in the folding pathway, and its structured core (a "nucleus") are distinguished by their essential influence on the folding/unfolding kinetics. In the second part of the paper, a theory of protein folding rates and related phenomena is presented. First it is shown that the protein size determines the range of a proteins folding rates in the vicinity of the point of thermodynamic equilibrium between the native and denatured states of the protein. Then, we present methods for calculating folding and unfolding rates of globular proteins from their sizes, stabilities and either 3D structures or amino acid sequences. Finally, we show that the same theory outlines ihe location of the protein folding nucleus (ie., the structured part of the transition, state) in reasonable agreement with experimental data.

Original languageEnglish
Pages (from-to)521-536
Number of pages16
JournalCurrent Protein and Peptide Science
Volume8
Issue number6
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

Keywords

  • Denatured Proteins
  • Folding nucleus
  • Folding Pathways
  • Molten globule
  • Mutant protein

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