Bound Water and Hydroxyproline are the essential contributors to collagen molecular stability: A Computational Analysis

Being the primarily organic phase of bone, collagen type I is an important contributor to bone’s mechanical resistance to fracture. Gaining mechanistic insight into collagen stabilization mechanism is critical to developing new targets to prevent bone fracture. The role of water and hydroxyproline (Hyp) in collagen stability mechanism is still controversial. The aim of this study was to investigate the influences of Hyp and bound water on the collagen molecular stability. Four collagen like-peptide (CLP) models were compared in terms of conformational energies and hydrogen bonding types. CLP1 model represents regular collagen structure without water molecules while CLP2 model represents collagen structure without water and Hyp residue. CLPW1 and CLPW2 are the models of CLP1 and CLP2 with water molecules around them, respectively. Cumulative interpreting of four CLPs models was shed light on the factors influencing collagen stability in the frame of steric energy. Total steric energy was ordered as: CLP2 > CLP1 > CLPW2 > CLPW1, indicating that CLPW1 was the most stable collagen model. On the other hand, CLP2 was the least stable collagen model based on the steric energy comparison. In addition, the hydrogen bonding observed in the four models reveled that water molecules around the models help in binding collagen triple helix through different water bridges since they contributed extra way for binding of triple chains. Moreover, some of the observed water bridges involved directly the presence of Hyp residue. Cumulative results suggested the important role of bound water molecules and Hyp on collagen molecular stability.