Role of proline …︁ proline interactions in the packing of collagenlike poly(tripeptide) triple helices

Conformational energy computations were carried out on the packing of two identical collagenlike poly(tripeptide) triple helices in order to determine the energetics of favorable packing arrangements as a function of composition and chain length. The triple helices considered were [CH₃CO-(Gly-Pro-Pro)_nt-NHCH₃]₃ and [CH₃CO-(Gly-Pro-Ala)_nt-NHCH₃]₃, with n_t = 3, 4, and 5. The packing arrangements were characterized in terms of their intermolecular energies and orientation angles Ω₀ of the axes of the two triple helices. For short triple helices (n_t = 3 or 4), many low-energy orientations, with a wide range of values of Ω₀, can occur. When the triple helices are longer (n_t = 5), the only low-energy packing arrangements of two poly(Gly-Pro-Pro) triple helices are those with a nearly parallel orientation of the two helix axes, with Ω₀ ≈ ?10°. This result accounts for the observed parallel (rather than antiparallel) arrangement of collagen molecules in microfibril assembly and stands in contrast to the preferred antiparallel arrangement of a pair of α-helices. Since the preference for a parallel arrangement of these collagenlike triple helices is less pronounced in the case of poly(Gly-Pro-Ala), it appears that this preference is a consequence of the frequent presence of imino acids in position Y of the Gly-X-Y repeating triplet. In poly(Gly-Pro-Ala), most of the low-energy packing arrangements are parallel, but a few arrangements with low energies and high values of |Ω₀| occur. These packing arrangements have a high energy, however, when Pro is substituted for Ala, and thus they are not accessible for collagen with natural amino (imino) acid sequences. The computations reported here account for some of the characteristic features of collagen packing in terms of the local interaction energies of a pair of triple helices.