title: The beta-strand-loop-beta-strand conformation is marginally populated in beta2-microglobulin (20-41) peptide in solution as revealed by replica exchange molecular dynamics simulations.
abstract: Solid-state NMR study shows that the 22-residue K3 peptide (Ser(20)-Lys(41)) from beta(2)-microglobulin (beta(2)m) adopts a beta-strand-loop-beta-strand conformation in its fibril state. Residue Pro(32) has a trans conformation in the fibril state of the peptide, while it adopts a cis conformation in the native state of full-length beta(2)m. To get insights into the structural properties of the K3 peptide, and determine whether the strand-loop-strand conformation is encoded at the monomeric level, we run all-atom explicit solvent replica exchange molecular dynamics on both the cis and trans variants. Our simulations show that the conformational space of the trans- and cis-K3 peptides is very different, with 1% of the sampled conformations in common at room temperature. In addition, both variants display only 0.3-0.5% of the conformations with beta-strand-loop-beta-strand character. This finding, compared to results on the Alzheimer's Abeta peptide, suggests that the biases toward aggregation leading to the beta-strand-loop-beta-strand conformation in fibrils are peptide-dependent.
authors.affiliation: National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai, China.
authors.forename: Chungwen
authors.initials: C
authors.lastname: Liang
authors.forename: Philippe
authors.initials: P
authors.lastname: Derreumaux
authors.forename: Normand
authors.initials: N
authors.lastname: Mousseau
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
mesh_terms: D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D012996:Solutions; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D010455:Peptides; D011506:Proteins; D012996:Solutions; D001613:beta 2-Microglobulin