Early assembly pathways of type I collagen

A method was developed for computing the free energy (delta Fi) of aggregates of type I collagen. The method was based on a treatment of Matheson and Flory describing phase equilibria of rigid rod polymers. It included a polymer-solvent interaction term that depended on near neighbor transfer energies. Extrahelical portions of the molecule were assigned local interaction energies differing from that assigned to the helix. Free energies of reaction for successive steps along assembly pathways (delta Fi-i+1) were computed. When allowance was made for specific pairing between extrahelical and helical domains, the so-called D-staggered (D = 670 A) alignment of molecules was preferred, as opposed to a nonstaggered, or nematic, alignment. Based on delta Fi-i+1 alone, it appeared that 1D-staggered oligomers arise first in assembly, followed later by addition of molecules in 4D alignment. Neither 4D dimers nor 4D-8D trimers were predicted to be major intermediates in assembly. This result is contrary to previous hypotheses. When energies of activation were included in the analysis, the prediction was less certain, and specific circumstances were identified in which 4D dimers and 4D-8D trimers were the earliest aggregated species in assembly.