Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin.

Water is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation of water molecules within a binding pocket. Recently, we developed the WaterDock protocol that was able to predict 97% of the water molecules in a test set. However, this approach generated false positives at a rate of over 20% in most cases and whilst this might be acceptable for some applications, in high throughput scenarios this is not desirable. Here we tackle this problem via the inclusion of knowledge regarding the solvation structure of ligand functional groups. We call this new protocol WaterDock2 and demonstrate that this protocol maintains a similar true positive rate to the original implementation but is capable of reducing the false-positive rate by over 50%. To improve the usability of the method, we have also developed a plugin for the popular graphics program PyMOL. The plugin also contains an implementation of the original WaterDock.GAR is supported by the Memorial Sloan Kettering Cancer Center, NIH grant P30 CA008748

Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin.

Water is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation of water molecules within a binding pocket. Recently, we developed the WaterDock protocol that was able to predict 97% of the water molecules in a test set. However, this approach generated false positives at a rate of over 20% in most cases and whilst this might be acceptable for some applications, in high throughput scenarios this is not desirable. Here we tackle this problem via the inclusion of knowledge regarding the solvation structure of ligand functional groups. We call this new protocol WaterDock2 and demonstrate that this protocol maintains a similar true positive rate to the original implementation but is capable of reducing the false-positive rate by over 50%. To improve the usability of the method, we have also developed a plugin for the popular graphics program PyMOL. The plugin also contains an implementation of the original WaterDock.GAR is supported by the Memorial Sloan Kettering Cancer Center, NIH grant P30 CA008748

On improving the selection of Thellier-type paleointensity data

The selection of paleointensity data is a challenging, but essential step for establishing data reliability. There is, however, no consensus as to how best to quantify paleointensity data and which data selection processes are most effective. To address these issues, we begin to lay the foundations for a more unified and theoretically justified approach to the selection of paleointensity data. We present a new compilation of standard definitions for paleointensity statistics to help remove ambiguities in their calculation. We also compile the largest‐to‐date data set of raw paleointensity data from historical locations and laboratory control experiments with which to test the effectiveness of commonly used sets of selection criteria. Although most currently used criteria are capable of increasing the proportion of accurate results accepted, criteria that are better at excluding inaccurate results tend to perform poorly at including accurate results and vice versa. In the extreme case, one widely used set of criteria, which is used by default in the ThellierTool software (v4.22), excludes so many accurate results that it is often statistically indistinguishable from randomly selecting data. We demonstrate that, when modified according to recent single domain paleointensity predictions, criteria sets that are no better than a random selector can produce statistically significant increases in the acceptance of accurate results and represent effective selection criteria. The use of such theoretically derived modifications places the selection of paleointensity data on a more justifiable theoretical foundation and we encourage the use of the modified criteria over their original forms

Advancing Precambrian palaeomagnetism with the PALEOMAGIA and PINT(_QPI) databases.

State-of-the-art measurements of the direction and intensity of Earth's ancient magnetic field have made important contributions to our understanding of the geology and palaeogeography of Precambrian Earth. The PALEOMAGIA and PINT(QPI) databases provide thorough public collections of important palaeomagnetic data of this kind. They comprise more than 4,100 observations in total and have been essential in supporting our international collaborative efforts to understand Earth's magnetic history on a timescale far longer than that of the present Phanerozoic Eon. Here, we provide an overview of the technical structure and applications of both databases, paying particular attention to recent improvements and discoveries

Palaeomagnetic field intensity variations suggest Mesoproterozoic inner-core nucleation

The Earth’s inner core grows by the freezing of liquid iron at its surface. The point in history at which this process initiated marks a step-change in the thermal evolution of the planet. Recent computational and experimental studies1,2,3,4,5 have presented radically differing estimates of the thermal conductivity of the Earth’s core, resulting in estimates of the timing of inner-core nucleation ranging from less than half a billion to nearly two billion years ago. Recent inner-core nucleation (high thermal conductivity) requires high outer-core temperatures in the early Earth that complicate models of thermal evolution. The nucleation of the core leads to a different convective regime6 and potentially different magnetic field structures that produce an observable signal in the palaeomagnetic record and allow the date of inner-core nucleation to be estimated directly. Previous studies searching for this signature have been hampered by the paucity of palaeomagnetic intensity measurements, by the lack of an effective means of assessing their reliability, and by shorter-timescale geomagnetic variations. Here we examine results from an expanded Precambrian database of palaeomagnetic intensity measurements7 selected using a new set of reliability criteria8. Our analysis provides intensity-based support for the dominant dipolarity of the time-averaged Precambrian field, a crucial requirement for palaeomagnetic reconstructions of continents. We also present firm evidence for the existence of very long-term variations in geomagnetic strength. The most prominent and robust transition in the record is an increase in both average field strength and variability that is observed to occur between a billion and 1.5 billion years ago. This observation is most readily explained by the nucleation of the inner core occurring during this interval9; the timing would tend to favour a modest value of core thermal conductivity and supports a simple thermal evolution model for the Earth

Microwave paleointensities indicate a low paleomagnetic dipole moment at the Permo-Triassic boundary

AbstractThe quantity of igneous material comprising the Siberian Traps provides a uniquely excellent opportunity to constrain Earth’s paleomagnetic field intensity at the Permo-Triassic boundary. There remains however, a contradiction about the strength of the magnetic field that is exacerbated by the limited number of measurement data. To clarify the geomagnetic field behavior during this time period, for the first time, a microwave paleointensity study has been carried out on the Permo-Triassic flood basalts in order to complement existing datasets obtained using conventional thermal techniques. Samples, which have been dated at ∼250Ma, of the Permo-Triassic trap basalts from the northern extrusive (Maymecha-Kotuy region) and the southeastern intrusive (areas of the Sytikanskaya and Yubileinaya kimberlite pipes) localities on the Siberian platform are investigated. These units have already demonstrated reliable paleomagnetic directions consistent with the retention of a primary remanence. Furthermore, Scanning Electron Microscope analysis confirms the presence of iron oxides likely of primary origin. Microwave Thellier-type paleointensity experiments (IZZI protocol with partial thermoremanent magnetization checks) are performed on 50 samples from 11 sites, of which, 28 samples from 7 sites provide satisfactory paleointensity data. The samples display corresponding distinct directional components, positive pTRM checks and little or no zig-zagging of the Arai or Zijderveld plot, providing evidence to support that the samples are not influenced by lab-induced alteration or multi-domain behavior. The accepted microwave paleointensity results from this study are combined with thermal Thellier-type results from previously published studies to obtain overall estimates for different regions of the Siberian Traps. The mean geomagnetic field intensity obtained from the samples of the northern part is 13.4±12.7μT (Maymecha-Kotuy region), whereas from the southeastern part is 17.3±16.5μT (Sytikanskaya kimberlite pipe) and 48.5±7.3μT (Yubileinaya kimberlite pipe), suggesting that the regional discrepancy is probably due to the insufficient sampling of geomagnetic secular variation, and thus, multiple localities need to be considered to obtain an accurate paleomagnetic dipole moment for this time period. It demonstrates that the overall mean paleointensity of the Siberian Traps is 19.5±13.0μT which corresponds to a mean virtual dipole moment of 3.2±1.8×1022Am2. Results indicate that the average magnetic field intensity during Permo-Triassic boundary is significantly lower (by approximately 50%) than the present geomagnetic field intensity, and thus, it implies that the Mesozoic dipole low might extend 50Myr further back in time than previously recognized

Актуальні проблеми розвитку виноградства та виноробства

В статті розглянуто сучасні тенденції та проблеми розвитку виноградарства та виноробства України. Надано рекомендації щодо пріоритетних напрямків розвитку виноробних підприємств.The modern tendencies and development problems of Ukraine viticulture and winemaking industry are considered in the article. The regards priority areas recommendations of winemaking enterprises development are given