949 research outputs found
Thermal detectors as X-ray spectrometers
Sensitive thermal detectors should be useful for measuring very small energy pulses, such as those produced by the absorption of X-ray photons. The measurement uncertainty can be very small, making the technique promising for high resolution nondispersive X-ray spectroscopy. The limits to the energy resolution of such thermal detectors are derived and used to find the resolution to be expected for a detector suitable for X-ray spectroscopy in the 100 eV to 10,000 eV range. If there is no noise in the thermalization of the X-ray, resolution better than 1 eV full width at half maximum is possible for detectors operating at 0.1 K. Energy loss in the conversion of the photon energy to heat is a potential problem. The loss mechanisms may include emission of photons or electrons, or the trapping of energy in long lived metastable states. Fluctuations in the phonon spectrum could also limit the resolution if phonon relaxation times are very long. Conceptual solutions are given for each of these possible problems
Coupling hydrophobic, dispersion, and electrostatic contributions in continuum solvent models
Recent studies of the hydration of micro- and nanoscale solutes have
demonstrated a strong {\it coupling} between hydrophobic, dispersion and
electrostatic contributions, a fact not accounted for in current implicit
solvent models. We present a theoretical formalism which accounts for coupling
by minimizing the Gibbs free energy with respect to a solvent volume exclusion
function. The solvent accessible surface is output of our theory. Our method is
illustrated with the hydration of alkane-assembled solutes on different length
scales, and captures the strong sensitivity to the particular form of the
solute-solvent interactions in agreement with recent computer simulations.Comment: 11 pages, 2 figure
From Zn to Mn: the study of novel manganese-binding groups in the search for new drugs against tuberculosis.
In most eubacteria, apicomplexans, and most plants, including the causal agents for diseases such as malaria, leprosy, and tuberculosis, the methylerythritol phosphate pathway is the route for the biosynthesis of the C(5) precursors to the essential isoprenoid class of compounds. Owing to their absence in humans, the enzymes of the methylerythritol phosphate pathway have become attractive targets for drug discovery. This work investigates a new class of inhibitors against the second enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase. Inhibition of this enzyme may involve the chelation of a crucial active site Mn ion, and the metal-chelating moieties studied here have previously been shown to be successful in application to the zinc-dependent metalloproteinases. Quantum mechanics and docking calculations presented in this work suggest the transferability of these metal-chelating compounds to Mn-containing 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme, as a promising starting point to the development of potent inhibitors
Functional dynamics of the folded ankyrin repeats of I kappa B alpha revealed by nuclear magnetic resonance.
Inhibition of nuclear factor kappaB (NF-kappaB) is mainly accomplished by IkappaB alpha, which consists of a signal response sequence at the N-terminus, a six-ankyrin repeat domain (ARD) that binds NF-kappaB, and a C-terminal PEST sequence. Previous studies with the ARD revealed that the fifth and sixth repeats are only partially folded in the absence of NF-kappaB. Here we report NMR studies of a truncated version of IkappaB alpha, containing only the first four ankyrin repeats, IkappaB alpha(67-206). This four-repeat segment is well-structured in the free state, enabling full resonance assignments to be made. H-D exchange, backbone dynamics, and residual dipolar coupling (RDC) experiments reveal regions of flexibility. In addition, regions consistent with the presence of micro- to millisecond motions occur periodically throughout the repeat structure. Comparison of the RDCs with the crystal structure gave only moderate agreement, but an ensemble of structures generated by accelerated molecular dynamics gave much better agreement with the measured RDCs. The regions showing flexibility correspond to those implicated in entropic compensation for the loss of flexibility in ankyrin repeats 5 and 6 upon binding to NF-kappaB. The regions showing micro- to millisecond motions in the free protein are the ends of the beta-hairpins that directly interact with NF-kappaB in the complex
Coupling nonpolar and polar solvation free energies in implicit solvent models
Recent studies on the solvation of atomistic and nanoscale solutes indicate
that a strong coupling exists between the hydrophobic, dispersion, and
electrostatic contributions to the solvation free energy, a facet not
considered in current implicit solvent models. We suggest a theoretical
formalism which accounts for coupling by minimizing the Gibbs free energy of
the solvent with respect to a solvent volume exclusion function. The resulting
differential equation is similar to the Laplace-Young equation for the
geometrical description of capillary interfaces, but is extended to microscopic
scales by explicitly considering curvature corrections as well as dispersion
and electrostatic contributions. Unlike existing implicit solvent approaches,
the solvent accessible surface is an output of our model. The presented
formalism is illustrated on spherically or cylindrically symmetrical systems of
neutral or charged solutes on different length scales. The results are in
agreement with computer simulations and, most importantly, demonstrate that our
method captures the strong sensitivity of solvent expulsion and dewetting to
the particular form of the solvent-solute interactions.Comment: accpted in J. Chem. Phy
Influence of conformational fluctuations on enzymatic activity: modelling the functional motion of beta-secretase
Considerable insight into the functional activity of proteins and enzymes can
be obtained by studying the low-energy conformational distortions that the
biopolymer can sustain. We carry out the characterization of these large scale
structural changes for a protein of considerable pharmaceutical interest, the
human -secretase. Starting from the crystallographic structure of the
protein, we use the recently introduced beta-Gaussian model to identify, with
negligible computational expenditure, the most significant distortion occurring
in thermal equilibrium and the associated time scales. The application of this
strategy allows to gain considerable insight into the putative functional
movements and, furthermore, helps to identify a handful of key regions in the
protein which have an important mechanical influence on the enzymatic activity
despite being spatially distant from the active site. The results obtained
within the Gaussian model are validated through an extensive comparison against
an all-atom Molecular Dynamics simulation.Comment: To be published in a special issue of J. Phys.: Cond. Mat. (Bedlewo
Workshop
Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>
Molecular and morphometric variation within and between population samples of the articulate brachiopod <i>Terebratulina</i> spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation
Statistical Mechanics of Torque Induced Denaturation of DNA
A unifying theory of the denaturation transition of DNA, driven by
temperature T or induced by an external mechanical torque Gamma is presented.
Our model couples the hydrogen-bond opening and the untwisting of the
helicoidal molecular structure. We show that denaturation corresponds to a
first-order phase transition from B-DNA to d-DNA phases and that the
coexistence region is naturally parametrized by the degree of supercoiling
sigma. The denaturation free energy, the temperature dependence of the twist
angle, the phase diagram in the T,Gamma plane and isotherms in the sigma, Gamma
plane are calculated and show a good agreement with experimental data.Comment: 5 pages, 3 figures, model improve
Kinetics of stochastically-gated diffusion-limited reactions and geometry of random walk trajectories
In this paper we study the kinetics of diffusion-limited, pseudo-first-order
A + B -> B reactions in situations in which the particles' intrinsic
reactivities vary randomly in time. That is, we suppose that the particles are
bearing "gates" which interchange randomly and independently of each other
between two states - an active state, when the reaction may take place, and a
blocked state, when the reaction is completly inhibited. We consider four
different models, such that the A particle can be either mobile or immobile,
gated or ungated, as well as ungated or gated B particles can be fixed at
random positions or move randomly. All models are formulated on a
-dimensional regular lattice and we suppose that the mobile species perform
independent, homogeneous, discrete-time lattice random walks. The model
involving a single, immobile, ungated target A and a concentration of mobile,
gated B particles is solved exactly. For the remaining three models we
determine exactly, in form of rigorous lower and upper bounds, the large-N
asymptotical behavior of the A particle survival probability. We also realize
that for all four models studied here such a probalibity can be interpreted as
the moment generating function of some functionals of random walk trajectories,
such as, e.g., the number of self-intersections, the number of sites visited
exactly a given number of times, "residence time" on a random array of lattice
sites and etc. Our results thus apply to the asymptotical behavior of the
corresponding generating functions which has not been known as yet.Comment: Latex, 45 pages, 5 ps-figures, submitted to PR
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