The contribution of pairwise amino-acid interactions to the stability of collagen triple helices has remained elusive. Progress in this area is critical for the prediction of triple helical stability from sequences and the preparation of mimetic materials based on this fold. Here we report a sequence-based scoring function for triple helices that takes into account the stability conferred to collagen by axial lysine–aspartate salt bridges. This function is used to predict the stability of a specific register formed from three distinct peptide sequences and that of all alternative compositions and registers. In the context of a genetic algorithm we use it to select sequences likely to self-assemble with high stability and to the exclusion of the other 26 possible combinations. We validate our methodology by synthesis and structural characterization of the designed peptides, which self-assemble into a highly stable ABC triple helix with control over both composition and register.. ? 2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
展开▼
