Molecular dynamic simulation studies on the effect of one residue chain staggering on the structure and stability of heterotrimeric collagen‐like peptides with interruption

Abstract

A systematic molecular dynamics (MD) simulation has been carried out on collagen-like peptides with different combinations of interruptions in the Gly-X(AA) -Y(AA) repeats. Although experimental studies have been carried out to elucidate the structural consequences of homotrimeric collagen-like peptides, this is the first report on the structural effect on the heterotrimeric models with G4G and G1G breaks present simultaneously in the constituent chains with difference in one residue chain staggering. The results reveal that the axial registry of the interrupted region changes significantly from that of conventional triple helical peptide without interruption. Further, results from MD simulations show the formation of a kink in the interrupted region of the triple-helical peptides. The conformational analysis reveals that the interruption in the Gly-X(AA) -Y(AA) pattern in these peptides induces β-strand conformation in triple helical peptides. The conventional hydrogen bonds in the interrupted triad are affected and new nonconventional H-bonds are formed in the triple helical structure, and as a result interrupted region becomes locally fragile. MM-PBSA calculations on the different systems clearly suggest that the binding affinity varies marginally due to one residue staggering. However, it is found from the structural parameters that hydrogen-bonding pattern differs significantly due to the difference in the staggering of chains.

Dynamic Heterogeneous Dielectric Generalized Born (DHDGB): An Implicit Membrane Model with a Dynamically Varying Bilayer Thickness

“…While experimental techniques have provided much of the available structural information, computer simulations of biological systems and of membrane proteins in particular have been able to provide critical information about the dynamics and energetics of these macromolecules. 4–6 …”

Unraveling the Role of Hydroxyproline in Maintaining the Thermal Stability of the Collagen Triple Helix Structure Using Simulation

“…In recent years, investigators have constructed fragments of collagen molecule to investigate problems that could not be solved by traditional studies. Singam et al reported that the structural effect on the heterotrimeric models with G4G and G1G breaks present simultaneously in the constituent chains with difference in one residue chain staggering and found that the structural parameters of the hydrogen-bonding pattern differ significantly due to the difference in the staggering of chains . Almora-Barrios et al used the Materials Studio, version 4.0 package to construct three chains of [ − OOC-(GLY-PRO-HYP) 10 -NH 2 + ] 3 folded into a triple-helix collagen fragment.…”

“…Singam et al reported that the structural effect on the heterotrimeric models with G4G and G1G breaks present simultaneously in the constituent chains with difference in one residue chain staggering and found that the structural parameters of the hydrogen-bonding pattern differ significantly due to the difference in the staggering of chains. 40 Almora-Barrios et al 41 used the Materials Studio, version 4.0 package to construct three chains of [ − OOC-(GLY-PRO-HYP) 10 -NH 2 + ] 3 folded into a triple-helix collagen fragment. By immersing the constructed collagen in a stoichiometric solution of Ca + , PO 4 3− , and OH − ions, they observed the formation of calcium phosphate clusters at the collagen template.…”

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