NDLI: Discriminating early stage Aβ42 monomer structures using chirality-induced 2DIR spectroscopy in a simulation study

Content Provider	PubMed Central
Author	Zhuang, Wei Sgourakis, Nikolaos G. Li, Zhenyu Garcia, Angel E. Shaul, Mukamel
Abstract	Elucidating the structural features of the Aβ 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 Aβ42 monomers is a mixture of diverse ordered and disordered conformational species, which can be classified according to the formation of a characteristic β-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 Aβ42 aggregation and open the possibility for their use as a novel experimental tool.
Related Links	http://dx.doi.org/10.1073/pnas.1002131107
Ending Page	15692
Page Count	6
Starting Page	15687
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	36
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-09-07
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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