Comparison of Structure Determination Methods for Intrinsically Disordered Amyloid-β Peptides

被引：49

作者：

Ball, K. Aurelia ^{[1
]}

Wemmer, David E. ^{[1
,2
]}

Head-Gordon, Teresa ^{[1
,2
,3
,4
]}

机构：

[1] Grad Grp Biophys, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA

[4] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2014年 / 118卷 / 24期

关键词：

PROTEIN-STRUCTURE DETERMINATION; FREE-ENERGY LANDSCAPE; UNSTRUCTURED PROTEINS; MOLECULAR-DYNAMICS; DIPOLAR COUPLINGS; CHEMICAL-SHIFTS; STATE ENSEMBLES; UNFOLDED STATE; C-TERMINUS; NMR;

D O I：

10.1021/jp410275y

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Intrinsically disordered proteins (IDPs) represent a new frontier in structural biology since the primary characteristic of IDPs is that structures need to be characterized as diverse ensembles of conformational substates. We compare two general but very different ways of combining NMR spectroscopy with theoretical methods to derive structural ensembles for the disease IDPs amyloid-beta 1-40 and amyloid-beta 1-42, which are associated with Alzheimer's Disease. We analyze the performance of de novo molecular dynamics and knowledge-based approaches for generating structural ensembles by assessing their ability to reproduce a range of NMR experimental observables. In addition to the comparison of computational methods, we also evaluate the relative value of different types of NMR data for refining or validating the IDP structural ensembles for these important disease peptides.

引用

页码：6405 / 6416

页数：12

共 83 条

[1] Determination of the Free Energy Landscape of α-Synuclein Using Spin Label Nuclear Magnetic Resonance Measurements [J].