Artikel,
Folding and misfolding of the collagen triple helix: Markov analysis of molecular dynamics simulations
BIOPHYSICAL JOURNAL, 93 (12): 4108-4115 (Dezember 2007)
DOI: {10.1529/biophysj.107.108100}
Zusammenfassung
Folding and misfolding of the collagen triple helix are studied through
molecular dynamics simulations of two collagenlike peptides,
(POG)(10)(3) and (POG)(4)POA(POG)(5)(3), which are models for
wild-type and mutant collagen, respectively. To extract long time
dynamics from short trajectories, we employ Markov state models. By
analyzing thermodynamic and kinetic quantities calculated from the
Markov state models, we examine folding mechanisms of the collagen
triple helix and consequences of glycine mutations. We find that the
C-to-N zipping of the collagen triple helix must be initiated by a
nucleation event consisting of formation of three stable hydrogen
bonds, and that zipping through a glycine mutation site requires a
renucleation event which also consists of formation of three stable
hydrogen bonds. Our results also suggest that slow kinetics, rather
than free energy differences, is mainly responsible for the stability
of the collagen triple helix.
