Thermodynamic control and dynamical regimes in protein folding

Abstract

Monte Carlo simulations of a simple lattice model of protein folding show two distinct regimes depending on the chain length. The first regime well describes the folding of small protein sequences and its kinetic counterpart appears to be single exponential in nature, while the second regime is typical of sequences longer than 80 amino acids and the folding performance achievable is sensitive to target conformation. The extent to which stability, as measured by the energy of a sequence in the target, is an essential requirement and affects the folding dynamics of protein molecules in the first regime is investigated. The folding dynamics of sequences whose design stage was restricted to a certain fraction of randomly selected amino acids shows that while some degree of stability is a necessary and sufficient condition for successful folding, designing sequences that provide the lowest energy in the target seems to be a superfluous constraint. By studying the dynamics of under annealed but otherwise freely designed sequences we explore the relation between stability and kinetic accessibility. We find that there is no one-to-one correspondence between having low energy and folding quickly to the target, as only a small fraction of the most stable sequences were also found to fold relatively quickly.

9 pages, 14 figures

References in corpus (2)

• Chain length scaling of protein folding time
• Statistical Analysis of Native Contact Formation in the Folding of Designed Model Proteins

Cited by in corpus (9)

• Identifying critical residues in protein folding: Insights from phi-value and Pfold analysis
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• Folding and form: Insights from lattice simulations
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• The Go model revisited: Native structure and the geometric coupling between local and long-range contacts
• Pathways to folding, nucleation events and native geometry
• Nucleation phenomena in protein folding: The modulating role of protein sequence
• Folding of small proteins: A matter of geometry?
• On the relation between native geometry and conformational plasticity