45 research outputs found
The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy
Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods
Improving Internal Peptide Dynamics in the Coarse-Grained MARTINI Model: Toward Large-Scale Simulations of Amyloid- and Elastin-like Peptides
We present an extension of the coarse-grained MARTINI
model for
proteins and apply this extension to amyloid- and elastin-like peptides.
Atomistic simulations of tetrapeptides, octapeptides, and longer peptides
in solution are used as a reference to parametrize a set of pseudodihedral
potentials that describe the internal flexibility of MARTINI peptides.
We assess the performance of the resulting model in reproducing various
structural properties computed from atomistic trajectories of peptides
in water. The addition of new dihedral angle potentials improves agreement
with the contact maps computed from atomistic simulations significantly.
We also address the question of which parameters derived from atomistic
trajectories are transferable between different lengths of peptides.
The modified coarse-grained model shows reasonable transferability
of parameters for the amyloid- and elastin-like peptides. In addition,
the improved coarse-grained model is also applied to investigate the
self-assembly of β-sheet forming peptides on the microsecond
time scale. The octapeptides SNNFGAIL and (GV)4 are used
to examine peptide aggregation in different environments, in water,
and at the water–octane interface. At the interface, peptide
adsorption occurs rapidly, and peptides spontaneously aggregate in
favor of stretched conformers resembling β-strands
Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study
Méthodologie multicritère d'aide à la décision pour les systèmes d'infiltration des eaux pluviales
Assessing the construct validity of five nutrient profiling systems using diet modeling with linear programming
International audienceNutrient profiling classifies individual food products according to their nutrient content. According to the WHO (World Health Organization), validation is a key step in the development of a nutrient profiling system. The aim was to assess the construct validity of five European nutrient profiling systems (Choices, Keyhole, (AFSSA), European Commission (EC) system and FoodProfiler). Construct validity was assessed for each of the five-selected nutrient profiling systems by testing whether healthy foods (that is, identified as eligible by the system) make healthy diets, and unhealthy foods (that is, non-eligible) make unhealthy diets, using diet modeling. The AFSSA, EC and FoodProfiler systems were identified as valid, but differences in their levels of permissiveness suggested some misclassified food products. The two other systems failed the construct validity assessment. Among these three systems, the EC system is the less demanding in terms of nutritional information, it would, therefore, be the easiest to implement for regulating nutrition and health claims in Europe