摘要 : Background: Aggregation of misfolded proteins under stress conditions in the cellmight lead to several neurodegenerative disorders. Amyloid-beta (Aβ_(1-42)) peptide, the causativeagent of Alzheimer’s disease, has the propensity to... 展开 Background: Aggregation of misfolded proteins under stress conditions in the cellmight lead to several neurodegenerative disorders. Amyloid-beta (Aβ_(1-42)) peptide, the causativeagent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, formingaggregated amyloid plaques. This is influenced by factors such as pH, temperature, metalions, mutation of residues, and ionic strength of the solution. There are several studies thathave highlighted the importance of ionic strength in affecting the folding and aggregationpropensity of Aβ_(1-42) peptide.Objective: To understand the effect of ionic strength of the solution on the aggregation propensityof Aβ_(1-42) peptide, using computational approaches.Materials and Methods: In this study, Molecular Dynamics (MD) simulations were performedon Aβ_(1-42) peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentrationof NaCl solution. To prepare the input files for the MD simulations, we have used theAmberff99SB force field. The conformational dynamics of Aβ_(1-42) peptide monomer in differentionic strengths of the solutions were illustrated from the analysis of the correspondingMD trajectory using the CPPtraj tool.Results: From the MD trajectory analysis, we observe that with an increase in the ionicstrength of the solution, Aβ_(1-42) peptide monomer shows a lesser tendency to undergo aggregation.From RMSD and SASA analysis, we noticed that Aβ_(1-42) peptide monomer undergoesa rapid change in conformation with an increase in the ionic strength of the solution. In addition,from the radius of gyration (Rg) analysis, we observed Aβ_(1-42) peptide monomer to bemore compact at moderate ionic strength of the solution. Aβ_(1-42) peptide was also found tohold its helical secondary structure at moderate and higher ionic strengths of the solution.The diffusion coefficient of Aβ_(1-42) peptide monomer was also found to vary with the ionicstrength of the solution. We observed a relatively higher diffusion coefficient value for Aβ_(1-42)peptide at moderate ionic strength of the solution.Conclusion: Our findings from this computational study highlight the marked effect of ionicstrength of the solution on the conformational dynamics and aggregation propensity of Aβ_(1-42)peptide monomer. 收起