High-Resolution Structures of the Amyloid-β 1-42 Dimers from the Comparison of Four Atomistic Force Fields.

ABSTRACT: The dimer of the amyloid-β peptide Aβ of 42 residues is the smallest toxic species in Alzheimer's disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn, and AMBERsb14 force fields with the TIP3P water model. On the basis of 144 μs replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties, and small-angle X-ray scattering profiles independent of the force field. There are, however, marked differences in secondary structure, with the AMBERsb14 and CHARMM22* ensembles overestimating the CD-derived helix content, and the OPLS-AA and AMBER

SUBMITTER: Man VH 

PROVIDER: S-EPMC5944325 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature