6 research outputs found
Основні підходи до розроблення дизайну упаковки
Упаковка – останній призов, який бачить покупець, і останній шанс
переконати його купити товар [1], тому над розробленням цікавого,
оригінального дизайну упаковки працює ціла армія професіоналів.
Дизайн упаковки включає гармонічну сукупність таких елементів, як:
форма, матеріал, розміри, якість виготовлення, вид друку, кольори
Sequence-Specific Mapping of the Interaction between Urea and Unfolded Ubiquitin from Ensemble Analysis of NMR and Small Angle Scattering Data
The molecular details of how urea interacts with, and
eventually
denatures proteins, remain largely unknown. In this study we have
used extensive experimental NMR data, in combination with statistical
coil ensemble modeling and small-angle scattering, to analyze the
conformational behavior of the protein ubiquitin in the presence of
urea. In order to develop an atomic resolution understanding of the
denatured state, conformational ensembles of full-atom descriptions
of unfolded proteins, including side chain conformations derived from
rotamer libraries, are combined with random sampling of explicit urea
molecules in interaction with the protein. Using this description
of the conformational equilibrium, we demonstrate that the direct-binding
model of urea to the protein backbone is compatible with available
experimental data. We find that, in the presence of 8 M urea, between
30 and 40% of the backbone peptide groups bind a urea molecule, independently
reproducing results from a model-free analysis of small-angle neutron
and X-ray scattering data. Crucially, this analysis also provides
sequence specific details of the interaction between urea and the
protein backbone. The pattern of urea-binding along the amino-acid
sequence reveals a higher level of binding in the central part of
the protein, a trend which resembles independent results derived from
chemical shift mapping of the urea–protein interaction. Together
these results substantiate the direct-binding model and provide a
framework for studying the physical basis of interactions between
proteins and solvent molecules
Mapping the Potential Energy Landscape of Intrinsically Disordered Proteins at Amino Acid Resolution
Intrinsically disordered regions are predicted to exist
in a significant fraction of proteins encoded in eukaryotic genomes.
The high levels of conformational plasticity of this class of proteins
endows them with unique capacities to act in functional modes not
achievable by folded proteins, but also places their molecular characterization
beyond the reach of classical structural biology. New techniques are
therefore required to understand the relationship between primary
sequence and biological function in this class of proteins. Although
dependences of some NMR parameters such as chemical shifts (CSs) or
residual dipolar couplings (RDCs) on structural propensity are known,
so that sampling regimes are often inferred from experimental observation,
there is currently no framework that allows for a statistical mapping
of the available Ramachandran space of each amino acid in terms of
conformational propensity. In this study we develop such an approach,
combining highly efficient conformational sampling with ensemble selection
to map the backbone conformational sampling of IDPs on a residue specific
level. By systematically analyzing the ability of NMR data to map
the conformational landscape of disordered proteins, we identify combinations
of RDCs and CSs that can be used to raise conformational degeneracies
inherent to different data types, and apply these approaches to characterize
the conformational behavior of two intrinsically disordered proteins,
the K18 domain from Tau protein and N<sub>TAIL</sub> from measles
virus nucleoprotein. In both cases, we identify the enhanced populations
of turn and helical regions in key regions of the proteins, as well
as contiguous strands that show clear and enhanced polyproline II
sampling
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale