Molecular Dynamics Simulation to Investigate Structural Characteristics of Aggrecan in Degenerated Intervertebral Discs

Abstract

Purpose Intervertebral discs (IDs) in human and animalbackbones resist compression and shear due to the nucleuspulposus (NP). The NP is mainly composed of water andaggrecan protein. As humans age, IDs degenerate, andaggrecan and water in the NP decrease; however, the relativewater density with respect to fixed aggrecan density increases. In this paper, changes in aggrecan’s structure with respect tochanges in water density in the NP were explored. Methods The atomic coordinates in aggreacan were takenfrom the Protein Data Bank. The molecular dynamicssimulation was implemented by using NAMD and VMDsoftwares 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 hydrogenbonds increase, the RMSD(root-mean-square density) ofamino acid residues decrease, and random coil secondarystructures with low RMSD appears, as the thickness of waterboxes increase from 6 to 30 Å. Conclusions According to the simulation study, as therelative water density in NP increases, highly fluctuatingsecondary structures are changed into low-fluctuation andlow-energy random coil structures.