Enhanced conformational space sampling improves the prediction of chemical shifts in proteins.

A biased-potential molecular dynamics simulation method, accelerated molecular dynamics (AMD), was combined with the chemical shift prediction algorithm SHIFTX to calculate (1)H(N), (15)N, (13)Calpha, (13)Cbeta, and (13)C' chemical shifts of the ankyrin repeat protein IkappaBalpha (residues 67-206), the primary inhibitor of nuclear factor kappa-B (NF-kappaB). Free-energy-weighted molecular ensembles were generated over a range of acceleration levels, affording systematic enhancement of the conformational space sampling of the protein. We have found that the predicted chemical shifts, particularly for the (15)N, (13)Calpha, and (13)Cbeta nuclei, improve substantially with enhanced conformational space sampling up to an optimal acceleration level. Significant improvement in the predicted chemical shift data coincides with those regions of the protein that exhibit backbone dynamics on longer time scales. Interestingly, the optimal acceleration level for reproduction of the chemical shift data has previously been shown to best reproduce the experimental residual dipolar coupling (RDC) data for this system, as both chemical shift data and RDCs report on an ensemble and time average in the millisecond range

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

The UMIST Database for Astrochemistry 2012

We present the fifth release of the UMIST Database for Astrochemistry (UDfA). The new reaction network contains 6173 gas-phase reactions, involving 467 species, 47 of which are new to this release. We have updated rate coefficients across all reaction types. We have included 1171 new anion reactions and updated and reviewed all photorates. In addition to the usual reaction network, we also now include, for download, state-specific deuterated rate coefficients, deuterium exchange reactions and a list of surface binding energies for many neutral species. Where possible, we have referenced the original source of all new and existing data. We have tested the main reaction network using a dark cloud model and a carbon-rich circumstellar envelope model. We present and briefly discuss the results of these models

Atmospheric and oceanic impacts of Antarctic glaciation across the Eocene-Oligocene transition

The glaciation of Antarctica at the Eocene–Oligocene transition (approx. 34 million years ago) was a major shift in the Earth’s climate system, but the mechanisms that caused the glaciation, and its effects, remain highly debated. A number of recent studies have used coupled atmosphere–ocean climate models to assess the climatic effects of Antarctic glacial inception, with often contrasting results. Here, using the HadCM3L model, we show that the global atmosphere and ocean response to growth of the Antarctic ice sheet is sensitive to subtle variations in palaeogeography, using two reconstructions representing Eocene and Oligocene geological stages. The earlier stage (Eocene; Priabonian), which has a relatively constricted Tasman Seaway, shows a major increase in sea surface temperature over the Pacific sector of the Southern Ocean in response to the ice sheet. This response does not occur for the later stage (Oligocene; Rupelian), which has a more open Tasman Seaway. This difference in temperature response is attributed to reorganization of ocean currents between the stages. Following ice sheet expansion in the earlier stage, the large Ross Sea gyre circulation decreases in size. Stronger zonal flow through the Tasman Seaway allows salinities to increase in the Ross Sea, deep-water formation initiates and multiple feedbacks then occur amplifying the temperature response. This is potentially a model-dependent result, but it highlights the sensitive nature of model simulations to subtle variations in palaeogeography, and highlights the need for coupled ice sheet–climate simulations to properly represent and investigate feedback processes acting on these time scales

The Dynamic Structure of Thrombin in Solution

AbstractThe backbone dynamics of human α-thrombin inhibited at the active site serine were analyzed using R1, R2, and heteronuclear NOE experiments, variable temperature TROSY 2D [1H-15N] correlation spectra, and Rex measurements. The N-terminus of the heavy chain, which is formed upon zymogen activation and inserts into the protein core, is highly ordered, as is much of the double beta-barrel core. Some of the surface loops, by contrast, remain very dynamic with order parameters as low as 0.5 indicating significant motions on the ps-ns timescale. Regions of the protein that were thought to be dynamic in the zymogen and to become rigid upon activation, in particular the γ-loop, the 180s loop, and the Na+ binding site have order parameters below 0.8. Significant Rex was observed in most of the γ-loop, in regions proximal to the light chain, and in the β-sheet core. Accelerated molecular dynamics simulations yielded a molecular ensemble consistent with measured residual dipolar couplings that revealed dynamic motions up to milliseconds. Several regions, including the light chain and two proximal loops, did not appear highly dynamic on the ps-ns timescale, but had significant motions on slower timescales

A Suite of Early Eocene (~55 Ma) Climate Model Boundary Conditions

We describe a set of early Eocene (~ 55 Ma) climate model boundary conditions constructed in a self-consistent reference frame and incorporating recent data and methodologies. Given the growing need for uniform experimental design within the Eocene climate modelling community and the challenges faced in simulating the prominent features of Eocene climate, we make publicly available our data sets of Eocene topography, bathymetry, tidal dissipation, vegetation, aerosol distributions and river runoff. Major improvements in our boundary conditions over previous efforts include the implementation of the ANTscape palaeotopography of Antarctica, more accurate representations of the Drake Passage and Tasman Gateway, as well as an approximation of sub grid cell topographic variability. Our boundary conditions also include for the first time modelled estimates of Eocene aerosol distributions and tidal dissipation, both consistent with our palaeotopography and palaeobathymetry. The resolution of our data sets is unprecedented and will facilitate high resolution climate simulations. In light of the inherent uncertainties involved in reconstructing global boundary conditions for past time periods these data sets should be considered as one interpretation of the available data and users are encouraged to modify them according to their needs and interpretations. This paper marks the beginning of a process for reconstructing a set of accurate, open-access Eocene boundary conditions for use in climate models

On the evolution of the molecular line profiles induced by the propagation of C-shock waves

We present the first results of the expected variations of the molecular line emission arising from material recently affected by C-shocks (shock precursors). Our parametric model of the structure of C-shocks has been coupled with a radiative transfer code to calculate the molecular excitation and line profiles of shock tracers such as SiO, and of ion and neutral molecules such as H13CO+ and HN13C, as the shock propagates through the unperturbed medium. Our results show that the SiO emission arising from the early stage of the magnetic precursor typically has very narrow line profiles slightly shifted in velocity with respect to the ambient cloud. This narrow emission is generated in the region where the bulk of the ion fluid has already slipped to larger velocities in the precursor as observed toward the young L1448-mm outflow. This strongly suggests that the detection of narrow SiO emission and of an ion enhancement in young shocks, is produced by the magnetic precursor of C-shocks. In addition, our model shows that the different velocity components observed toward this outflow can be explained by the coexistence of different shocks at different evolutionary stages, within the same beam of the single-dish observations.Comment: 7 pages, 4 figures, accepted for publication in Ap

Palaeogeographic controls on climate and proxy interpretation

During the period from approximately 150 to 35?million years ago, the Cretaceous–Paleocene–Eocene (CPE), the Earth was in a “greenhouse” state with little or no ice at either pole. It was also a period of considerable global change, from the warmest periods of the mid-Cretaceous, to the threshold of icehouse conditions at the end of the Eocene. However, the relative contribution of palaeogeographic change, solar change, and carbon cycle change to these climatic variations is unknown. Here, making use of recent advances in computing power, and a set of unique palaeogeographic maps, we carry out an ensemble of 19 General Circulation Model simulations covering this period, one simulation per stratigraphic stage. By maintaining atmospheric CO2 concentration constant across the simulations, we are able to identify the contribution from palaeogeographic and solar forcing to global change across the CPE, and explore the underlying mechanisms. We find that global mean surface temperature is remarkably constant across the simulations, resulting from a cancellation of opposing trends from solar and palaeogeographic change. However, there are significant modelled variations on a regional scale. The stratigraphic stage–stage transitions which exhibit greatest climatic change are associated with transitions in the mode of ocean circulation, themselves often associated with changes in ocean gateways, and amplified by feedbacks related to emissivity and planetary albedo. We also find some control on global mean temperature from continental area and global mean orography. Our results have important implications for the interpretation of single-site palaeo proxy records. In particular, our results allow the non-CO2 (i.e. palaeogeographic and solar constant) components of proxy records to be removed, leaving a more global component associated with carbon cycle change. This “adjustment factor” is used to adjust sea surface temperatures, as the deep ocean is not fully equilibrated in the model. The adjustment factor is illustrated for seven key sites in the CPE, and applied to proxy data from Falkland Plateau, and we provide data so that similar adjustments can be made to any site and for any time period within the CPE. Ultimately, this will enable isolation of the CO2-forced climate signal to be extracted from multiple proxy records from around the globe, allowing an evaluation of the regional signals and extent of polar amplification in response to CO2 changes during the CPE. Finally, regions where the adjustment factor is constant throughout the CPE could indicate places where future proxies could be targeted in order to reconstruct the purest CO2-induced temperature change, where the complicating contributions of other processes are minimised. Therefore, combined with other considerations, this work could provide useful information for supporting targets for drilling localities and outcrop studies

Mid-infrared spectra of PAH emission in Herbig AeBe stars

We present spectra of four Herbig AeBe stars obtained with the Infrared Spectrograph (IRS). on the Spitzer Space Telescope. All four of the sources show strong emission from polycyclic aromatic hydrocarbons (PAHs), with the 6.2 um emission feature shifted to 6.3 um and the strongest C-C skeletal-mode feature occuring at 7.9 um instead of at 7.7 um as is often seen. Remarkably, none of the four stars have silicate emission. The strength of the 7.9 um feature varies with respect to the 11.3 um feature among the sources, indicating that we have observed PAHs with a range of ionization fractions. The ionization fraction is higher for systems with hotter and brighter central stars. Two sources, HD 34282 and HD 169142, show emission features from aliphatic hydrocarbons at 6.85 and 7.25 um. The spectrum of HD 141569 shows a previously undetected emission feature at 12.4 um which may be related to the 12.7 um PAH feature. The spectrum of HD 135344, the coolest star in our sample, shows an unusual profile in the 7-9 um region, with the peak emission to the red of 8.0 um and no 8.6 um PAH feature.Comment: Accepted by ApJ 23 June, 2005, 8 pages (emulateapj), 5 figures (3 in color

Morphology of Shocked Lateral Outflows in Colliding Hydrodynamic Flows

Supersonic interacting flows occurring in phenomena such as protostellar jets give rise to strong shocks, and have been demonstrated in several laboratory experiments. To study such colliding flows, we use the AstroBEAR AMR code to conduct hydrodynamic simulations in three dimensions. We introduce variations in the flow parameters of density, velocity, and cross sectional radius of the colliding flows %radius in order to study the propagation and conical shape of the bow shock formed by collisions between two, not necessarily symmetric, hypersonic flows. We find that the motion of the interaction region is driven by imbalances in ram pressure between the two flows, while the conical structure of the bow shock is a result of shocked lateral outflows (SLOs) being deflected from the horizontal when the flows are of differing cross-section