Scaling approach to the folding kinetics of large proteins

Erik D. Nelson, Nick V. Grishin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We study a nucleation-growth model of protein folding and extend it to describe larger proteins with multiple folding units. The model is of one of an extremely simple type in which amino acids are allowed just two states-either folded (frozen) or unfolded. Its energetics are heterogeneous and Gō-like, the energy being defined in terms of the number of atom-to-atom contacts that would occur between frozen amino acids in the native crystal structure of the protein. Each collective state of the amino acids is intended to represent a small free energy microensemble consisting of the possible configurations of unfolded loops, open segments, and free ends constrained by the cross-links that form between folded parts of the molecule. We approximate protein free energy landscapes by an infinite subset of these microensemble topologies in which loops and open unfolded segments can be viewed roughly as independent objects for the purpose of calculating their entropy, and we develop a means to implement this approximation in Monte Carlo simulations. We show that this approach describes transition state structures (values) more accurately and identifies folding intermediates that were unavailable to previous versions of the model that restricted the number of loops and nuclei.

Original languageEnglish (US)
Article number011904
JournalPhysical Review E - Statistical, Nonlinear, and Soft Matter Physics
Volume73
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Folding
folding
Amino Acids
Kinetics
Scaling
proteins
Protein
amino acids
scaling
Free Energy
kinetics
Transition State
Energy Landscape
Protein Folding
free energy
Crystal Structure
Growth Model
Nucleation
Nucleus
Monte Carlo Simulation

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Condensed Matter Physics
  • Statistical and Nonlinear Physics
  • Mathematical Physics

Cite this

Scaling approach to the folding kinetics of large proteins. / Nelson, Erik D.; Grishin, Nick V.

In: Physical Review E - Statistical, Nonlinear, and Soft Matter Physics, Vol. 73, No. 1, 011904, 01.2006.

Research output: Contribution to journalArticle

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