title: Essential dynamics of reversible peptide folding: memory-free conformational dynamics governed by internal hydrogen bonds.
abstract: A principal component analysis has been applied on equilibrium simulations of a beta-heptapeptide that shows reversible folding in a methanol solution. The analysis shows that the configurational space contains only three dense sub-states. These states of relatively low free energy correspond to the "native" left-handed helix, a partly helical intermediate, and a hairpin-like structure. The collection of unfolded conformations form a relatively diffuse cloud with little substructure. Internal hydrogen-bonding energies were found to correlate well with the degree of folding. The native helical structure folds from the N terminus; the transition from the major folding intermediate to the native helical structure involves the formation of the two most C-terminal backbone hydrogen bonds. A four-state Markov model was found to describe transition frequencies between the conformational states within error limits, indicating that memory-effects are negligible beyond the nanosecond time-scale. The dominant native state fluctuations were found to be very similar to unfolding motions, suggesting that unfolding pathways can be inferred from fluctuations in the native state. The low-dimensional essential subspace, describing 69% of the collective atomic fluctuations, was found to converge at time-scales of the order of one nanosecond at all temperatures investigated, whereas folding/unfolding takes place at significantly longer time-scales, even above the melting temperature.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Theoretical Molecular Biophysics Group, Göttingen, Germany.
authors.forename: B L
authors.initials: BL
authors.lastname: de Groot
authors.forename: X
authors.initials: X
authors.lastname: Daura
authors.forename: A E
authors.initials: AE
authors.lastname: Mark
authors.forename: H
authors.initials: H
authors.lastname: Grubmüller
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D008390:Markov Chains; D000432:Methanol / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013696:Temperature; D013816:Thermodynamics
chemical_list: D010455:Peptides; D000432:Methanol