Effects of Hydroxylation and Packing Geometry on Tropocollagen Stability: Insights from Molecular Dynamics Simulations.

Collagen is the most prevalent protein in living organisms, playing diverse roles across multiple tissues. Its hierarchical structure relies on the assembly of tropocollagen, the fundamental building block of collagen fibrils. This assembly occurs in a predominantly random manner, allowing for variations in packing. This randomness can lead to regions of both tight and nontight packing within the fibrils. The mechanisms by which these regions influence collagen's packing configurations, structural organization, and functional properties remain poorly understood. This study provides a focused investigation by comparing tight packing (hexameric) and less tight (heptameric) tropocollagen configurations enriched with proline or hydroxyproline residues using molecular dynamics simulations. The results indicate that the hexameric structures are more stable and uniform because their strands fit together well. This close packing allows for better hydrogen bonding, strengthening their connections. In contrast, adding a seventh strand in the heptameric structures creates asymmetry. This disrupts the hydrogen bonding, leading to weaker connections and a less stable structure. We also found that hydroxyproline-rich systems exhibit greater global mobility due to enhanced water interactions while maintaining local structural rigidity through increased intermolecular hydrogen bonding. In contrast, proline-rich systems display greater flexibility at the residue level but reduced overall molecular movement, indicating a more rigid global structure. This distinction between tropocollagen assemblies and their composition offers invaluable insights into the molecular basis of collagen stability and functionality.