Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2010-9-8
pubmed:abstractText
Elucidating the structural features of the Abeta monomer, the peptide constituent of amyloid fibrils found in Alzheimer's disease, can enable a direct characterization of aggregation pathways. Recent studies support the view that the ensemble of Abeta42 monomers is a mixture of diverse ordered and disordered conformational species, which can be classified according to the formation of a characteristic beta-hairpin conformation in a certain region. Despite the disparity in the structural features of these species, commonly used spectroscopic techniques such as NMR may not directly trace the conformational dynamics in the ensemble due to the limited time resolution and the lack of well-resolved spectral features for different comformers. Here we use molecular dynamics simulations combined with simulations of two-dimensional IR (2DIR) spectra to investigate the structure of these species, their interchange kinetics, and their spectral features. We show that while the discrimination efficiency of the ordinary, nonchiral 2DIR signal is limited due to its intrinsic dependence on common order parameters that are dominated by the generally unstructured part of the sequence, signals with carefully designed chirality-sensitive pulse configurations have the high resolution required for differentiating the various monomer structures. Our combined simulation studies indicate the power of the chirality-induced (CI) 2DIR technique in investigating early events in Abeta42 aggregation and open the possibility for their use as a novel experimental tool.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-10940221, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-11159381, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-11722581, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-12130773, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-12481027, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-12506200, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-12511861, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-14971932, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-15758995, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-15800619, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16040800, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16045764, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-1613791, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16211538, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16293696, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16501222, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16503636, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-16537487, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17008529, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17046788, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17122853, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17146054, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17397862, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-1749933, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-17675411, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-18078331, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-18499799, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-19346479, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-19496555, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-19815514, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-2881207, http://linkedlifedata.com/resource/pubmed/commentcorrection/20798063-9348659
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15687-92
pubmed:dateRevised
2011-7-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Discriminating early stage A{beta}42 monomer structures using chirality-induced 2DIR spectroscopy in a simulation study.
pubmed:affiliation
Dalian Institute of Chemical Physics, Liaoning, China. wzhuang@dicp.ac.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural