Journal
PROTEIN SCIENCE
Volume 15, Issue 3, Pages 420-428Publisher
WILEY
DOI: 10.1110/ps.051762406
Keywords
structure; mass spectrometry; correlation of structure with spectra and other properties; new methods; computational analysis of protein structure; molecular dynamics
Categories
Ask authors/readers for more resources
The structural properties of the A beta 42 peptide, a main constituent of the amyloid plaques formed in Alzheimer's disease, were investigated through a combination of ion-mobility mass spectrometry and theoretical modeling. Replica exchange molecular dynamics simulations using a fully atomic description of the peptide and implicit water solvent were performed on the -3 charge state of the peptide, its preferred state under experimental conditions. Equilibrated structures at 300 K were clustered into three distinct families with similar structural features within a family and with significant root mean square deviations between families. An analysis of secondary structure indicates the A beta 42 peptide conformations are dominated by loops and turns but show some helical structure in the C-terminal hydrophobic tail. A second calculation on A beta 42 in a solvent-free environment yields compact structures turned inside out from the solution structures (hydrophobic parts on the outside, polar parts on the inside). Ion mobility experiments on the A beta 42-3 charge state electrosprayed from solution yield a bimodal arrival time distribution. This distribution can be quantitatively fit using cross-sections from dehydrated forms of the three families of calculated solution structures and the calculated solvent-free family of structures. Implications of the calculations on the early stages of aggregation of A beta 42 are discussed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available