Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward

Concentration and partitioning of heavy metals in the Scheldt estuary

The continuous growth of technology has lead to an (uncontrolled) introduction of contaminants into the biosphere. The efforts of removing man-made pollutants from the natural environment have been unable to cope with the increasing amounts of waste materials and growing population. This work studies one group of substances which have a particular lasting effect on the natural balance in aquatic systems; the heavy metals. Trace metals are present in all the abiotic reservoirs of the aquatic systems; i.e. the water, the suspended material and the sediments and its pore waters. Complexation of the dissolved metals with organic and inorganic ligands, sorption and biological processes are the main processes determining the distribution of the investigated metals (Cd, Cu, Hg, Pb and Zn) between the dissolved and particulate phase under oxic conditions. Under anoxic conditions, sulphide precipitation controls the behaviour of the investigated metals. Chemical processes occurring at the solid-water interface greatly influence the geochemical cycles of many elements, as well as the composition of natural waters and the flux of material through the hydrosphere. A theoretical description based on the surface complexation model, the competitive adsorption model and sulphide precipitation, was used to model the behaviour of the investigated heavy metals in the Scheldt estuary. Different analytical techniques: AAS, XRF, ASV, were optimized and used for the experimental determination of the heavy metals in the different abiotic reservoirs and their partitioning between the dissolved and particulate phase. An intercomparison exercise was carried out to investigate the possibility of determining elemental concentrations in very small amounts (1-5 mg) of natural suspended material after acid digestion. Results show that the precision and accuracy of the analytical procedure are mainly limited by inhomogeneities inherent to natural suspended material. Great difficulties were encountered for the determination of Cu in estuarine and marine water. The digestion of the organic material by UV and micro wave radiation improved the accuracy of the measurement, but the problem could not be solved entirely. For the determination of Hg in sediments, investigation of the extraction techniques and of the possible interferences during measurement, showed that Hg could be determined with satisfactory accuracy and precision using cold vapour AAS. The heavy metals content of the sediments, the suspended material and the water of the Scheldt estuary and part of the North Sea were investigated. Several normalization methods showed that the sediments of the Belgian North Sea and the Scheldt estuary are polluted with the heavy metals Zn, Cd, Pb and Hg, with average enrichment factors between 2 and 10. This pollution becomes extreme in the industrial part of the Scheldt where enrichment factors for a single sample can reach up to e.g. 130 for Cd. These maxima occur for each of the four elements. Cu and Ni do not show such an enrichment in most of the sediments of the area. The pollution level of the North Sea and harbour sediments seems to be controlled by the same factors; these sediments form a population for which grain size is the more important factor controlling the heavy metal content. This was proven by the obtained regression lines, correlation analysis and the analysis of the fraction 109Cd were investigated using natural particulate material from the Scheldt estuary .The desorption of Cu from polluted sediments is very slow. Only at high salinities, minor desorption was detected. At persistently low pH (109Cd on natural particulate material from the Scheldt estuary changes as a function of temperature, salinity and composition of the particulate material. The temperature has only a minor influence on the Kd-salinity relation, while the composition of the suspended matter appeared to be very important. Even though the number of samples used was very low, preliminary results do show that the organic content of the sediments may be the most important parameter for the Cd adsorption. The similar relation between the Kd of the adsorption process, measured using 109Cd and the desorption process as a function of salinity, indicates that character of the metal-sediment binding of the adsorbed 109Cd may be identical to that of the naturally bound Cd which is released during the desorption process. The magnitude of the Kd, however, needs to be determined taking into account the different environmental parameters. Comparison of the calculated and measured dissolved Cd, Hg and Pb concentrations in the Scheldt estuary under anoxic conditions shows that these concentrations cannot be described by sulphide precipitation and complexation reactions. The conditions of anoxicity in the estuary cannot be compared to the conditions present in a permanently anoxic basin. The dissolved Cu concentrations can be described using sulphide precipitation and complexation if Cu+ is used as the dominant Cu-species. The model calculations show that the dissolved Zn concentration could be reasonably well explained by sulphide precipitation and complexation. During oxic conditions, the use of average input parameters gives a reasonably good agreement between the measured Kd values in the field and the calculated values for Cd and Zn. The calculated values for Cu, Hg and Pb are generally too high compared to the measured ones, which implies that the use of the Ki and N may be unrealistic. To validate the model properly it is of primary importance to construct a database containing all the experimentally determined input parameters, so that the use of average values can be avoided. The model explains well the observed trends and there is generally little difference in the calculated values when the surface complexation concepts were or were not used. Both models result in similar relations and magnitudes for the Kd values. It is possible that the used dissolved phase for the laboratory experiments does not contain the organic ligands determined by Van den Berg et al. (1987) since these solutions were obtained by mixing open sea water with riverine water. Van den Berg et al. (1987) investigated real estuarine water, while our solutions only approximate the concentrations of the components which behave conservatively during estuarine mixing. No conservative behaviour of the dissolved organic ligands has so far been reported for the Scheldt estuary. When no organic ligands were included the model explains well the obtained Kd-salinity relation for Cu and Zn for the desorption experiments

The Challenging World of Simple Inorganic Rings:Revisiting Roesky's Ketone and Roesky's Sulfoxide

The surprising differences between the experimental solid-state and calculated gas-phase structures of 5-oxo-1,3,2,4-dithiadiazole (Roesky's ketone, 1) and 1-oxo-1,2,4,3,5-trithiadiazole (Roesky's sulfoxide, 2), identified and studied in a series of papers published between 2004 and 2010 but then never satisfactorily explained, have been revisited, making use of the more advanced computational possibilities currently available. The previous calculations’ considerable overestimations of the C−S and S−S bond lengths in 1 and 2, respectively, have been partly explained based on the results of periodic calculations and the application of Valence Bond (VB) Theory. In the case of 1, the crystal environment appears to stabilize a structure with a highly polarized C=O bond, which features a C−S bond with considerable double-bond character – an effect which does not exist for the isolated molecule – explaining the much shorter bond in the solid state. For 2, a similar conclusion can be drawn for the S−S distance. For both compounds, though, packing effects are not the sole source of the differences: the inability of Density Functional Theory (DFT) to properly deal with the electronic structures of these apparently simple main-group systems remains a contributing factor.</p