The Impact Of Charged Surface On The Aggregation Structures Of Polypeptides:A Molecular Dynamics Simulation Study

Amyloid fibrils,which is self-assembled from protein or peptides,is the main pathology of Alzheimer's disease?Huntington's disease and other neurodegenerative disease.It was found the A? peptides existed in the meningeal cells of Alzheimer's patients and such peptides could self-assembled into a complex structure,called amyloid fibrils.Through the comprehensive study of the self-assembly mechanism of amyloid fibrils,on the one hand,the prevention and treatment of neurodegenerative disease will be developed.On the other hand,amyloid fibrils is a potential novel biomaterial because of its excellent and mechanical properties.It was found that ?-sheet was the main secondary structure of amyloid fibrils.In order to reveal the selfassembly mechanism of amyloid fibrils,the mechanism of self-assembly processes of peptides into ?-sheet should be studied first.The self-assembly processes of peptides into ?-sheet are dependent on various of factors such as size of the peptide aggregates,characteristics of the substrate,and solution conditions such as temperature and electrolyte concentration.In this paper,we systematically performed molecular dynamics simulations to study self-assembly processes of A?(16-22)peptides in pure water and at a CH3-terminated hydrophobic SAM surface and a negatively charged acetyl-terminated SAM,so that the effect of charged surface on the self-assembly processes of peptides was elucidated.First,the effect of the magnitude of charge of aqueous-solid interfaces on the self-assembly processes of peptides was study.Several molecular dynamics simulations of self-assembly processes of A?(16-22)peptides at the negatively charged acetyl-terminated SAM,whose magnitude of charge was 1:5,1:4,1:3,1:2 and 1:1,were performed respectively,and a detailed analysis and discussion was carried out later.When the magnitude of charge of interface is low,peptides self-assemble into a compact aggregate due to lack of the magnitude of charge of interface.Peptides self-assemble into a multi-layered ?-sheet at the negatively charged acetylterminated SAM.Besides that,the percentage of ?-sheet increases along with the increase of the magnitude of charge of aqueous-solid interfaces.Interestingly,the percentage of ?-sheet is also high at the low magnitude of charge of interfaces.That is because peptides self-assemble into a compact globular-like aggregate at such aqueous-solid interfaces.Furtherly,the effect of the negatively charged aqueous-solid interfaces on the selfassembly processes of peptides was study.In this part,we performed several molecular dynamics simulations to study the self-assembly processes of peptides in pure water and at a CH3-terminated hydrophobic SAM surface and a negatively charged acetyl-terminated SAM,whose magnitude of charged was 1:1,and a detailed analysis and discussion was also carried out latter.Comparing with the self-assembly processes of peptides in pure water and at a CH3-terminated hydrophobic SAM surface,the negatively charged acetyl-terminated SAM significantly promotes the formation of ?-sheet.Besides that,different alignment of aggregate was achieved in each system.In pure water,a random orientation of peptides in most directions accept the Z axis is achieved because of gravity.At a CH3-terminated hydrophobic SAM surface,peptides tend to orient parallel to the hydrophobic interface.Most importantly,peptides upright relative to the SAM surface and side by side with each other that promotes the formation of backbone hydrogen bonds and hence the ?-sheets.