Molecular dynamics simulation to investigate structural characteristics of aggrecan in degenerated intervertebral discs

Purpose: Intervertebral discs (IDs) in human and animal backbones resist compression and shear due to the nucleus pulposus (NP). The NP is mainly composed of water and aggrecan protein. As humans age, IDs degenerate, and aggrecan and water in the NP decrease; however, the relative water density with respect to fixed aggrecan density increases. In this paper, changes in aggrecan’s structure with respect to changes in water density in the NP were explored. Methods: The atomic coordinates in aggreacan were taken from the Protein Data Bank. The molecular dynamics simulation was implemented by using NAMD and VMD softwares To investigate the effect of water density in the NP, we used cubic water boxes with thickness 6, 20, and 30 Å. Results: We found that the number of hydrophilic hydrogen bonds increase, the RMSD(root-mean-square density) of amino acid residues decrease, and random coil secondary structures with low RMSD appears, as the thickness of water boxes increase from 6 to 30 Å. Conclusions: According to the simulation study, as the relative water density in NP increases, highly fluctuating secondary structures are changed into low-fluctuation and low-energy random coil structures.