Relazione tra Composizione e Proprietà della Proteina Collagene Attraverso Simulazioni Quanto meccaniche

Collagen is one of the most abundant proteins in mammals and it is the building block of complex hierarchical structures such as bones and tendons.[1] Structurally, it is composed by three parallel polypeptide strands wrapped up together to form a triple helix. The primary structure of a collagen strand is mainly the repetition of an amino acidic triplet of Gly-X-Y type, which occurs in all types of collagens. In each triplet, glycine (Gly) always occupies the first position, while X and Y position could be in principle occupied by every amino acid. However, the most common amino acid in X position is a Proline (Pro), while in Y position is a Hydroxyproline (Hyp), thus making the Gly-Pro-Hyp composition the most abundant one (10.5%).[2] The understanding of the effect of composition on collagen's properties is essential within the field of collagen-engineering. This can help finding stable and biocompatible compositions that could be the starting point for the development of new biomaterials.[3] Even if a lot of effort have been made experimentally[4] to elucidate each amino acid propensity to the formation of the triple helix, the reasons of these composition-stability relationship at a molecular level are still not clear. A possible way out may could be using DFT molecular simulation. This technique of investigation combines atomic resolution and accuracy, and it is a useful tool for studying biological systems. Unfortunately, the limited size of the investigable systems with this approach makes it rarely employed in protein science. Thanks to highly symmetrical collagen protein models, we reduced the computational cost of our calculations. In this way we succeeded in applying this technique for studying collagen protein. We investigated the role of the amino acid in X position in affecting the geometry, stability and elastic properties of Gly-X-Hyp-type helices. Our results are in good agreement with experimental ones. From the analyses of our data we shed some light on the physicochemical reasons for the features of different compositions. [1] Bella, J. Collagen Structure : New Tricks from a Very Old Dog. Biochem. J. 2016, 473, 1001¿1025. [2] Ramshaw, J. A. M.; Shah, N. K.; Brodsky, B. Gly-X-Y Tripeptide Frequencies in Collagen: A Context for Host-Guest Triple-Helical Peptides. J. Struct. Biol. 1998, 122 (1¿2), 86¿91. [3] Zhang, Y.; Malamakal, R. M.; Chenoweth, D. M. Aza-Glycine Induces Collagen Hyperstability. J. Am. Chem. Soc 2015, 137, 12422−12425. [4] Persikov, A. V.; Ramshaw, J. A. M.; Kirkpatrick, A.; Brodsky, B. Amino Acid Propensities for the Collagen Triple-Helix. Biochemistry 2000, 39 (48), 14960¿14967.