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Complexity in protein folding: Simulation meets experiment

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A. Caflisch; P. Hamm

Journal: Curr. Phys. Chem.
Year: 2012
Volume: 2
Issue: 1
Pages: 4-11
DOI: 10.2174/1877946811202010004
Type of Publication: Journal Article

Backbone; Cross-linked alpha-helix; Free energy surface of folding; Kinetic Partitioning; Misfolded traps; molecular dynamics simulations; peptide; Protein Folding; Steric Encumbrance; Time-resolved infrared spectroscopy


We review our joint experimental-theoretical effort on the folding of photo-switchable α-helices. The folding kinetics of these peptides is profoundly non-exponential, which is attributed to a partitioning of the unfolded state into several misfolded traps. These traps are connected to the folded state in a hub-like fashion with folding barriers of different heights. Molecular dynamics simulations reveal a semi-quantitative agreement with the complex response observed in the experiment, allowing one to discuss the process in unprecedented detail. It is found that the nonexponential response is to a large extent introduced by the photo-linker used to initiate folding. Hence, folding of these cross-linked peptides emulates formation of a helical segment in the context of a globular protein rather than folding of an isolated peptide.