1,784 research outputs found
Buried and accessible surface area control intrinsic protein flexibility
Proteins experience a wide variety of conformational dynamics that can be
crucial for facilitating their diverse functions. How is the intrinsic
flexibility required for these motions encoded in their three-dimensional
structures? Here, the overall flexibility of a protein is demonstrated to be
tightly coupled to the total amount of surface area buried within its fold. A
simple proxy for this, the relative solvent accessible surface area (Arel),
therefore shows excellent agreement with independent measures of global protein
flexibility derived from various experimental and computational methods.
Application of Arel on a large scale demonstrates its utility by revealing
unique sequence and structural properties associated with intrinsic
flexibility. In particular, flexibility as measured by Arel shows little
correspondence with intrinsic disorder, but instead tends to be associated with
multiple domains and increased {\alpha}- helical structure. Furthermore, the
apparent flexibility of monomeric proteins is found to be useful for
identifying quaternary structure errors in published crystal structures. There
is also a strong tendency for the crystal structures of more flexible proteins
to be solved to lower resolutions. Finally, local solvent accessibility is
shown to be a primary determinant of local residue flexibility. Overall this
work provides both fundamental mechanistic insight into the origin of protein
flexibility and a simple, practical method for predicting flexibility from
protein structures.Comment: 36 pages, 11 figures, author's manuscript, accepted for publication
in Journal of Molecular Biolog
Land Grant Application- Marsh, Joseph (Westminister)
Land grant application submitted to the Maine Land Office on behalf of Joseph Marsh for service in the Revolutionary War, by their widow Mary.https://digitalmaine.com/revolutionary_war_mass/1226/thumbnail.jp
Constraints on primordial magnetic fields from CMB distortions in the axiverse
Measuring spectral distortions of the cosmic microwave background (CMB) is
attracting considerable attention as a probe of high energy particle physics in
the cosmological context, since PIXIE and PRISM have recently been proposed. In
this paper, CMB distortions due to resonant conversions between CMB photons and
light axion like particles (ALPs) are investigated, motivated by the string
axiverse scenario which suggests the presence of a plenitude of light axion
particles. Since these resonant conversions depend on the strength of
primordial magnetic fields, constraints on CMB distortions can provide an upper
limit on the product of the photon-ALP coupling constant g and the comoving
strength of primordial magnetic fields B. Potentially feasible constraints from
PIXIE/PRISM can set a limit g B < 10^{-16} GeV^{-1} nG for ALP mass, m_\phi <
10^{-14} eV. Although this result is not a direct constraint on g and B, it is
significantly tighter than the product of the current upper limits on g and B.Comment: 8 pages, 3 figure
Distributional Impacts of Country-of-Origin Labeling in the U.S. Meat Industry
Concerns about the negative effects of U.S. meat and livestock imports on domestic livestock prices have increased interest in country-of origin labeling (COOL) legislation. An equilibrium displacement model is used to estimate short-run and long-run changes in equilibrium prices and quantities of meat and livestock in the beef, pork, and poultry sectors resulting from the implementation of COOL. Retail beef and pork demand would have to experience a one-time, permanent increase of 4.05% and 4.45%, respectively, so that feeder cattle and hog producers do not lose producer surplus over a 10-year period.country-of-origin labeling, equilibrium displacement model, producer surplus, Agribusiness,
A 3.55 keV Photon Line and its Morphology from a 3.55 keV ALP Line
Galaxy clusters can efficiently convert axion-like particles (ALPs) to
photons. We propose that the recently claimed detection of a 3.55--3.57 keV
line in the stacked spectra of a large number of galaxy clusters and the
Andromeda galaxy may originate from the decay of either a scalar or fermionic
keV dark matter species into an axion-like particle (ALP) of mass , which subsequently converts to a photon in
the cluster magnetic field. In contrast to models in which the photon line
arises directly from dark matter decay or annihilation, this can explain the
anomalous line strength in the Perseus cluster. As axion-photon conversion
scales as and cool core clusters have high central magnetic fields, this
model can also explains the observed peaking of the line emission in the cool
cores of the Perseus, Ophiuchus and Centaurus clusters, as opposed to the much
larger dark matter halos. We describe distinctive predictions of this scenario
for future observations.Comment: 6 page
Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations
Abstract To deal with the huge number of novel protein‐coding variants identified by genome and exome sequencing studies, many computational variant effect predictors (VEPs) have been developed. Such predictors are often trained and evaluated using different variant data sets, making a direct comparison between VEPs difficult. In this study, we use 31 previously published deep mutational scanning (DMS) experiments, which provide quantitative, independent phenotypic measurements for large numbers of single amino acid substitutions, in order to benchmark and compare 46 different VEPs. We also evaluate the ability of DMS measurements and VEPs to discriminate between pathogenic and benign missense variants. We find that DMS experiments tend to be superior to the top‐ranking predictors, demonstrating the tremendous potential of DMS for identifying novel human disease mutations. Among the VEPs, DeepSequence clearly stood out, showing both the strongest correlations with DMS data and having the best ability to predict pathogenic mutations, which is especially remarkable given that it is an unsupervised method. We further recommend SNAP2, DEOGEN2, SNPs&GO, SuSPect and REVEL based upon their performance in these analyses
Galaxy UV-luminosity function and reionization constraints on axion dark matter
If the dark matter (DM) were composed of axions, then structure formation in
the Universe would be suppressed below the axion Jeans scale. Using an analytic
model for the halo mass function of a mixed DM model with axions and cold dark
matter, combined with the abundance-matching technique, we construct the
UV-luminosity function. Axions suppress high- galaxy formation and the
UV-luminosity function is truncated at a faintest limiting magnitude. From the
UV-luminosity function, we predict the reionization history of the universe and
find that axion DM causes reionization to occur at lower redshift. We search
for evidence of axions using the Hubble Ultra Deep Field UV-luminosity function
in the redshift range -, and the optical depth to reionization,
, as measured from cosmic microwave background polarization. All probes
we consider consistently exclude from
contributing more than half of the DM, with our strongest constraint ruling
this model out at more than significance. In conservative models of
reionization a dominant component of DM with is in
tension with the measured value of , putting pressure on an
axion solution to the cusp-core problem. Tension is reduced to for
the axion contributing only half of the DM. A future measurement of the
UV-luminosity function in the range - by JWST would provide further
evidence for or against . Probing still higher masses
of will be possible using future measurements of the
kinetic Sunyaev-Zel'dovich effect by Advanced ACTPol to constrain the time and
duration of reionization.Comment: 17 pages, 8 figures, 2 tables. v2: Minor Changes. References added.
Published in MNRA
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