Energy landscapes of a hairpin peptide including NMR chemical shift restraints.

Methods recently introduced to improve the efficiency of protein structure prediction simulations by adding a restraint potential to a molecular mechanics force field introduce additional input parameters that can affect the performance. Here we investigate the changes in the energy landscape as the relative weight of the two contributions, force field and restraint potential, is systematically altered, for restraint functions constructed from calculated nuclear magnetic resonance chemical shifts. Benchmarking calculations were performed on a 12-residue peptide, tryptophan zipper 1, which features both secondary structure (a β-hairpin) and specific packing of tryptophan sidechains. Basin-hopping global optimization was performed to assess the efficiency with which lowest-energy structures are located, and the discrete path sampling approach was employed to survey the energy landscapes between unfolded and folded structures. We find that inclusion of the chemical shift restraints improves the efficiency of structure prediction because the energy landscape becomes more funnelled and the proportion of local minima classified as native increases. However, the funnelling nature of the landscape is reduced as the relative contribution of the chemical shift restraint potential is increased past an optimal value.This research was supported by the EPSRC and the ERC.This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5CP01259

Future evolution of the Sahel precipitation zonal contrast in CESM1

The main focus of this study is the zonal contrast of the Sahel precipitation shown in the CMIP5 climate projections: precipitation decreases over the western Sahel (i.e., Senegal and western Mali) and increases over the central Sahel (i.e., eastern Mali, Burkina Faso and Niger). This zonal contrast in future precipitation change is a robust model response to climate change but suffers from a lack of an explanation. To this aim, we study the impact of current and future climate change on Sahel precipitation by using the Large Ensemble of the Community Earth System Model version 1 (CESM1). In CESM1, global warming leads to a strengthening of the zonal contrast, as shown by the difference between the 2060–2099 period (under a high emission scenario) and the 1960–1999 period (under the historical forcing). The zonal contrast is associated with dynamic shifts in the atmospheric circulation. We show that, in absence of a forced response, that is, when only accounting for internal climate variability, the zonal contrast is associated with the Pacific and the tropical Atlantic oceans variability. However, future patterns in sea surface temperature (SST) anomalies are not necessary to explaining the projected strengthening of the zonal contrast. The mechanisms underlying the simulated changes are elucidated by analysing a set of CMIP5 idealised simulations. We show the increase in precipitation over the central Sahel to be mostly associated with the surface warming over northern Africa, which favour the displacement of the monsoon cell northwards. Over the western Sahel, the decrease in Sahel precipitation is associated with a southward shift of the monsoon circulation, and is mostly due to the warming of the SST. These two mechanisms allow explaining the zonal contrast in precipitation change

Research data supporting "Energy landscapes of a hairpin peptide including NMR chemical shift restraints"

In the top-level directory, there are two input files for CHARMM: (1) orderparams.inp -> to calculate quantities for a given structure used to obtain the structural order parameters (2) charmm_md.inp -> to run molecular dynamics simulations in two parts: an initial heating phase (commands commented out) and a constant-temperature production phaseThe four subdirectories alpha0/ alpha0.3/ alpha0.5/ and alpha0.7/ contain input and output files for the kinetic transition networks assembled using discrete path sampling for the four different overall potentials. These directories contain: (1) min.data -> database of minima in the kinetic transition network (2) ts.data -> database of transition states in the kinetic transition network (3) points.min -> coordinates of the minima in min.data (direct access, unformatted file) (4) points.ts -> coordinates of the transition states in ts.data (direct access, unformatted file) (5) min.A, min.B -> input files for PATHSAMPLE required for certain types of run (6) pathdata -> input file for the PATHSAMPLE program for discrete path sampling (7) odata.connect -> input file for running double-ended connections using the OPTIM program with CHARMM interfaced (8) 1le0_extended.pdb -> PDB file for an extended structure of the trpzip1 peptide, used as input to CHARMM and OPTIM with CHARMM interfaced (9) perm.allow -> input file used by OPTIM and PATHSAMPLE for the optimal alignment of pairs of structures with respect to overall translation, rotation and permutational isomerization (10) input.crd -> template input coordinates file based on CHARMM card format* (11) chemshifts.dat -> input file for OPTIM, containing the reference CamShift chemical shifts (NOT needed for forcefield only calculations, i.e. directory alpha0/) (12) dinfo -> input file for plotting disconnectivity graphs using the disconnectionDPS program Subdirectory basinhopping/ (1) data -> input file for the GMIN program with CHARMM interfaced, to show the options used (2) [1,2,3,4,5,6,7,8,9,10].dbase.1 -> output coordinate files, based on CHARMM card format*, containing the lowest-energy minimum found by GMIN in the 10 independent runs starting from different configurations (labelled by the run number) Running PATHSAMPLE with the current keywords will compute the "fastest" path through the network between the minima whose indices are specified in the min.A and min.B files, at 298K. The binary files can be read using the PATHSAMPLE program compiled with the NAG Fortran Compiler Release 6.0 (64 bit). * Input and output CHARMM coordinate files are formatted based on the CHARMM card format, for free-field reading, but with modifications to the source code to allow greater precision in the coordinates and longer line lengths (120 characters), found to be essential to our work.For the meaning and operation of specific keywords in the input files please refer to the user manuals (see http://www-wales.ch.cam.ac.uk/software.html and http://www.charmm.org/documentation/chmdoc.html). For further enquiries please email Prof. David J. Wales .This work was supported by the EPSRC [grant number EP/H042660/1] and ERC [grant number 267369]

Chromate reduction in highly alkaline groundwater by zerovalent iron: Implications for its use in a permeable reactive barrier

It is not currently known if the widely used reaction of zerovalent iron (ZVI) and Cr(VI) can be used in a permeable reactive barrier (PRB) to immobilize Cr leaching from hyperalkaline chromite ore processing residue (COPR). This study compares Cr(VI) removal from COPR leachate and chromate solution by ZVI at high pH. Cr(VI) removal occurs more rapidly from the chromate solution than from COPR leachate. The reaction is first order with respect to both [Cr(VI)] and the iron surface area, but iron surface reactivity is lost to the reaction. Buffering pH downward produces little change in the removal rate or the specific capacity of iron until acidic conditions are reached. SEM and XPS analyses confirm that reaction products accumulate on the iron surface in both liquors, but that other surface precipitates also form in COPR leachate. Leachate from highly alkaline COPR contains Ca, Si, and Al that precipitate on the iron surface and significantly reduce the specific capacity of iron to reduce Cr(VI). This study suggests that, although Cr(VI) reduction by ZVI will occur at hyperalkaline pH, other solutes present in COPR leachate will limit the design life of a PRB

Recent Arctic amplification and extreme mid-latitude weather

The Arctic region has warmed more than twice as fast as the global average — a phenomenon known as Arctic amplification. The rapid Arctic warming has contributed to dramatic melting of Arctic sea ice and spring snow cover, at a pace greater than that simulated by climate models. These profound changes to the Arctic system have coincided with a period of ostensibly more frequent extreme weather events across the Northern Hemisphere mid-latitudes, including severe winters. The possibility of a link between Arctic change and mid-latitude weather has spurred research activities that reveal three potential dynamical pathways linking Arctic amplification to mid-latitude weather: changes in storm tracks, the jet stream, and planetary waves and their associated energy propagation. Through changes in these key atmospheric features, it is possible, in principle, for sea ice and snow cover to jointly influence mid-latitude weather. However, because of incomplete knowledge of how high-latitude climate change influences these phenomena, combined with sparse and short data records, and imperfect models, large uncertainties regarding the magnitude of such an influence remain. We conclude that improved process understanding, sustained and additional Arctic observations, and better coordinated modelling studies will be needed to advance our understanding of the influences on mid-latitude weather and extreme events

Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding

The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex alpha 2,3- and alpha 2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of alpha 2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in human

Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding▿ ‡

The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans