Heterotrimeric collagen helix with high specificity of assembly results in a rapid rate of folding.

The most abundant natural collagens form heterotrimeric triple helices. Synthetic mimics of collagen heterotrimers have been found to fold slowly, even compared to the already slow rates of homotrimeric helices. These prolonged folding rates are not understood.

Cation-π Interactions and Their Role in Assembling Collagen Triple Helices.

Cation-π interactions play a significant role in the stabilization of globular proteins. However, their role in collagen triple helices is less well understood and they have rarely been used in de novo designed collagen mimetic systems. In this study, we analyze the stabilizing and destabilizing effects in pairwise amino acid interactions between cationic and aromatic residues in both axial and lateral sequential relationships.

Recent Advances in Collagen Mimetic Peptide Structure and Design.

Collagen mimetic peptides (CMPs) fold into a polyproline type II triple helix, allowing the study of the structure and function (or misfunction) of the collagen family of proteins. This Perspective will focus on recent developments in the use of CMPs toward understanding the structure and controlling the stability of the triple helix. Triple helix assembly is influenced by various factors, including the single amino acid propensity for the triple helix fold, pairwise interactions between these amino acids, and long-range effects observed across the helix, such as bend, twist, and fraying.

Predicting the stability of homotrimeric and heterotrimeric collagen helices.

Robust methods for predicting thermal stabilities of collagen triple helices are critical for understanding natural structure and stability in the collagen family of proteins and also for designing synthetic peptides mimicking these essential proteins. In this work, we determine the relative stability imparted on the collagen triple helix by single amino acids and interactions between amino acid pairs. Using this analysis, we create a comprehensive algorithm, SCEPTTr, for predicting melting temperatures of synthetic triple helices.

Covalent Capture of Collagen Triple Helices Using Lysine-Aspartate and Lysine-Glutamate Pairs.

Collagen mimetic peptides (CMPs) self-assemble into a triple helix reproducing the most fundamental aspect of the collagen structural hierarchy. They are therefore important for both further understanding this complex family of proteins and use in a wide range of biomaterials and biomedical applications. CMP self-assembly is complicated by a number of factors which limit the use of CMPs including their slow rate of folding, relatively poor monomer-trimer equilibrium, and the large number of competing species possible in heterotrimeric helices.