Background: Aggregation of misfolded proteins under stress conditions in the cell
might lead to several neurodegenerative disorders. Amyloid-beta (Aβ1-42) peptide, the causative
agent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, forming
aggregated amyloid plaques. This is influenced by factors such as pH, temperature, metal
ions, mutation of residues, and ionic strength of the solution. There are several studies that
have highlighted the importance of ionic strength in affecting the folding and aggregation
propensity of Aβ1-42 peptide.
Objective: To understand the effect of ionic strength of the solution on the aggregation propensity
of Aβ1-42 peptide, using computational approaches.
Materials and Methods: In this study, Molecular Dynamics (MD) simulations were performed
on Aβ1-42 peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentration
of NaCl solution. To prepare the input files for the MD simulations, we have used the
Amberff99SB force field. The conformational dynamics of Aβ1-42 peptide monomer in different
ionic strengths of the solutions were illustrated from the analysis of the corresponding
MD trajectory using the CPPtraj tool.
Results: From the MD trajectory analysis, we observe that with an increase in the ionic
strength of the solution, Aβ1-42 peptide monomer shows a lesser tendency to undergo aggregation.
From RMSD and SASA analysis, we noticed that Aβ1-42 peptide monomer undergoes
a 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 Aβ1-42 peptide monomer to be
more compact at moderate ionic strength of the solution. Aβ1-42 peptide was also found to
hold its helical secondary structure at moderate and higher ionic strengths of the solution.
The diffusion coefficient of Aβ1-42 peptide monomer was also found to vary with the ionic
strength of the solution. We observed a relatively higher diffusion coefficient value for Aβ1-42
peptide at moderate ionic strength of the solution.
Conclusion: Our findings from this computational study highlight the marked effect of ionic
strength of the solution on the conformational dynamics and aggregation propensity of Aβ1-42