Research Of Structural Dynamics And Vibrational Spectra Of Amyloid Peptide With GQD And C₂N

With the aged tendency of population develops rapidly,more and more people are suffering from Alzheimer’s disease（AD）,and bringing huge social and economic burden to the health care system.The scientific community has not given a definite explanation for the etiology of AD,and there are no very effective drugs to prevent the development of AD.The larger researchers begin to focus their attention on the detection,treatment and prevention of amyloid diseases with nanomaterials with good biocompatibility.Zero-dimensional materials-graphene quantum dots（GQD）and some two-dimensional materials have shown enormous potential in the treatment of AD and other protein folding conformation diseases.Nitrogenated holey graphene（C₂N）has become a potential candidate for biological and medical applications due to its mildness,attractiveness to immobilized proteins and biocompatibility.We hope to explore the mechanism of action between different fragments of GQD,nitrogenated holey graphene（C₂N）and Aβ,and the rules of action between them through theoretical calculation and molecular dynamics simulation,so as to provide some insights for the realization of depolymerization and inhibition of amyloid/polypeptide fibers and provide some new strategies for AD prevention and control.This paper surrounded the following three perspectives:With GQD and Aβ_37-42as the research objects,the molecular dynamics simulation was used to explore the possible intermolecular interactions between Aβ_37-42and GQD.The most probable conformation obtained by cluster analysis was identified by vibration spectrum.The effect of adsorption on the secondary structure conformation of Aβ_37-42,Aβ_37-42fragment changed from the initial irregular coil shape to the irregular coil and bend shape.The interaction of GQD and Aβ_37-42makes the frequency shift and conformation change of amide-I band.Studies have shown that GQD can inhibit Aβaggregation to some extent.Explore the structural dynamics behaviors of isolated Aβ_13-20and Aβ_13-20-C₂N in aqueous solution.The binding free energy was calculated.Revealed that there was a good affinity between Aβ_13-20and C₂N and the combination was stable.The effect of C₂N on the conformation of Aβ_13-20residue was analyzed by protein secondary structure diagram.DSSP diagram showed that Aβ_13-20in Aβ_13-20-C₂N system was more random coil conformation,and the proportion of bending conformation was reduced compared with Aβ_13-20system.The most probable conformations of Aβ_13-20obtained by cluster analysis were calculated by infrared spectroscopy.Cluster analysis showed that the basic residues LYS and HIS in Aβ_13-20could be closely combined with C₂N in periodic pores.At the same time,the amide-I band and-NH₃group on the skeleton of Aβ_13-20polypeptide were identified.The strong nucleophilic effect prompted C₂N to be more inclined to combine with-NH₃group on Aβ_13-20,and the combination was stable.The dynamic results of the structure selected from the clustering of the initial molecular simulation are the same as those of the initial structure.The absorption of Aβ_13-20is largely limited by its surface binding sites.Once it reaches there,its lateral translocation is highly restricted,showing a periodic binding center.The structural dynamic behavior of Aβ_37-42-C₂N in aqueous solution was studied by all-atom molecular dynamics simulation.The combined with the free energy calculation results showed that Aβ_37-42had good affinity with C₂N and the combination was stable.DSSP diagram showed that there was interaction between Aβ_37-42and C₂N,which could inhibit the transformation of Aβ_37-42to bend conformation to a certain extent.RDF analysis showed that Aβ_37-42tended to exhibit a stretch conformation under the influence of intermolecular hydrogen bonds.The infrared spectra of the most probable conformation of Aβ_37-42obtained by cluster analysis were calculated.The correlation between the conformation of Aβ_37-42and the vibration spectra was analyzed by identifying the amide-I band and-NH₃group on the polypeptide skeleton of Aβ_37-42.Because of the high negative charge in the C₂N periodic pore,the strong nucleophilic effect makes C₂N more inclined to combine with the-NH₃group on Aβ_37-42,thus affecting the conformation and frequency of Aβ_37-42.