Molecular Dynamics Simulation Of The Effect Of Lysine Residue Mutation On Aβ42 Self-Assembly

Alzheimer’s disease(AD)is one of the leading causes of dementia and is more common in the elderly.AD can lead to cognitive and mobility impairments in patients,and post-care needs to consume a lot of social resources,causing a great burden to the family and society.β-Amyloid peptide 42(Aβ42)is a fragment produced by the proteolytic cleavage of amyloid precursor protein(APP).It is a peptide containing 42 amino acid residues and is a type of amyloid.At present,the treatment of AD is mainly to reduce the accumulation of Aβ42 in the brain of patients.Due to the existence of β-sheet,Aβ42 self-assembles and aggregates to form oligomers.The toxicity of oligomers causes neurofibrillary tangles and deletions to lead to the formation of AD.Relevant studies have shown that the lysine residues at positions16 and 28 on the Aβ42 peptide chain are the factors that cause Aβ42 self-assembly.In this experiment,molecular dynamics simulations were used to investigate the effect of mutation of lysine residues(K)at positions 16 and 28 into glycine residues(G)on the self-assembly of Aβ42.WT Aβ42(Wild type)was used as the control group.The molecular dynamics simulations were carried out for the three systems respectively.Molecular dynamics simulation results showed that after 30 ns simulation,the root mean square deviations of the three systems are stable,and the stability of K16 G and K28 G is better than that of WT Aβ42.The root mean square fluctuation values of K16 G and K28 G were lower than those of WT Aβ42.The changes of the root mean square fluctuation values of the three systems further proved that the mutant K16 G and K28 G systems had better stability.The secondary structures of the K16 G and K28 G systems after mutation showed that the β-sheet content after self-assembly was significantly reduced,and was lower than that of WT Aβ42 after self-assembly.The mutation of lysine residues affects the self-assembly results of Aβ42,which significantly reduces the content of β-sheets in the secondary structure of Aβ42,and the mutated system is more stable.The reduction of β-sheets can theoretically alleviate the pathogenesis of AD.