Comparison of molecular dynamics simulation methods for amyloid β1–42 monomers containing d-aspartic acid residues for predicting retention times in chromatography

Molecular dynamics simulations of amyloid β1–42 containing d-aspartic acid residues were performed using several continuous solvent models to investigate the usefulness of simulation methods for d-amino acid-containing proteins and peptides. Normal molecular dynamics simulations and replica exchange molecular dynamics simulations, which are one of the generalized-ensemble algorithms, were performed. Because the β-structure contents of amyloid β1–42 peptides obtained by replica exchange molecular dynamics simulations with Onufriev–Bashford–Case generalized Born implicit solvent were qualitatively consistent with experimental data, replica exchange molecular dynamics rather than other methods appeared to be more reasonable for calculations of amyloid β1–42 containing d-aspartic acid residues. Computational results revealed that peptides with stereoinversion of Asp23 tend to form β-sheet structures by themselves, in contrast to the wild-type peptides that form β-sheet structures only after aggregation. These results are expected to be useful for computational investigations of proteins and peptides such as prediction of retention time of peptides and proteins containing d-aspartic acid residues.