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 beta(1-42) 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 beta-structure contents of amyloid beta(1-42) 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 beta(1-42) containing D-aspartic acid residues. Computational results revealed that peptides with stereoinversion of Asp23 tend to form beta-sheet structures by themselves, in contrast to the wild-type peptides that form beta-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. (C) 2011 Elsevier B.V. All rights reserved.