Understanding the role of stereoelectronic effects in determining collagen stability. 2. A quantum mechanical/molecular mechanical study of (proline-proline-glycine)n polypeptides

The importance of vicinal and long-range interresidue effects in detg. the stability of the collagen triple helix has been investigated by quantum mech. (QM) and mol. mech. (MM) computations on suitable model polypeptides, taking into account solvent effects by the polarizable continuum model (PCM). At the QM level, the PII conformation corresponds to an energy min. for pentapeptide analogs incorporating the sequence Gly-Pro-Pro-Gly, irresp. of the down or up puckering of the pyrrolidine ring. However, the authors' computations indicate that the alternation of down and up prolines characterizing collagen and collagen-like peptides is not due to an intrinsic preference of the Pro-Pro-Gly sequence. This result is confirmed by MM computations of longer polypeptides. Next, MM computations on model triple helixes show that a better packing is obtained for specific values of backbone dihedrals, which, in turn, favor the alternation of down and up prolines along each chain.