Role of Length-Dependent Stability of Collagen-like Peptides

Abstract

Understanding the structure, folding, and stability of collagen is complex because of its length and variations in the amino acid (AA) sequence composition. It is well known that the basic constituent of the collagen helix is the triplet repeating sequence of the form Gly-X(AA)-Y(AA). On the basis of previous models and with the frequency of occurrence of the triplets, the ((Gly-Pro-Hyp)n)3 (where n is the number of triplets) sequence replicate has been chosen as the model for the most stable form of the collagen-like sequence. With a view to understand the role of sequence length (or the number of triplets) on the stability of collagen, molecular dynamics simulations have been carried out by varying the number of triplet units on the model collagen-like peptides. The results reveal that five triplets are required to form the stable triple helix. Further analysis shows that the intermolecular structural rigidity of the imino acid residues, hydrogen bonding, and water structure around the three chains of the triple helix play the dominant roles on its structure, folding, and stabilization.

Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of Clostridium histolyticum Collagenase for Its Inhibition

“…Cooperative transition is the characteristic unfolding nature of collagen but the selected sequence results in monotonic transition. It suggests that the D Ala substituted collagen like peptide fails to form stable triple helical conformation which agrees with several authors, because at least of six triplets of GPO is necessary to form stable triple helix [ 52 , 64 – 67 ]. Melting profile of the D Ala substituted peptide is similar to its L-counterpart ( S1 Fig ) because the selected peptide sequence lacks in GPO repeats.…”

Does l to d-amino acid substitution trigger helix → sheet conformations in collagen like peptides adsorbed to surfaces?

“…Model peptides with the X AA -Y AA -Gly repeats have been widely used in the past to understand collagen folding, packing and in structural elucidation of unique triple helical conformation. Till date fibril forming collagen mimetic peptides have exploited hydroxyproline based, thermally stabilized sequences [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. Collagen like peptides provide an insight into the engineering of novel collagen like biomaterials.…”

On the multiscale modeling of heart valve biomechanics in health and disease

“…Few efforts do exist, however, that are directly applicable. In particular, research is carried out to simulate various aspects of the behavior of collagen fiber on the molecular-scale (Park et al 2007;Raman et al 2006Raman et al , 2008aSalsas-Escat and Stultz 2008).…”