a, b, Folding trajectories (shown at 2-ns intervals) of peptide models of native collagen and of a mutant bearing a GlySer substitution that models a mutation found in several forms of osteogenesis imperfecta. In b the relatively large Ser side chains prevent the peptide chains from packing closely together at the site of the mutation. c, Free-energy profiles for folding of the peptide models. For the peptide model with GlySer mutation, the calculated free energy of the more compact state at 3.4 Å is more than 20 kcal mol^-1 higher than that of the state at 5.7 Å, suggesting that folding to an ideal triple-helical structure at the site of mutation is unfavourable. d, Free-energy profiles for folding of the peptide T3-785 models. These data suggest that imino-poor segments from collagen can exist in two states: the native state corresponds to the crystallographically observed conformation, whereas in the vulnerable state the imino-poor segments of collagen are partially unfolded. For glycated collagens (mutated peptide T3-785), the energy of the vulnerable state is almost 1.3 kcal mol^-1 lower than that of the native state, suggesting that most of the glycated collagens molecules exist in a vulnerable state. e, Representative structures from states in d. (a and b are reprinted in part with permission from ref. 77; c is reprinted in part with permission from ref. 77. d and e are reprinted in part with permission from ref. 73.)]