Large scale deployment of molecular docking application on computational grid infrastructures for combating malaria

PCSVInternational audienceComputational grids are solutions for several biological applications like virtual screening or molecular dynamics where large amounts of computing power and storage are required. The WISDOM project successfully deployed virtual screening at large scale on EGEE grid infrastructures in the summer 2005 and achieved 46 million dockings in 45 days, which is equivalent to 80 CPU years. WISDOM is one good example of a successful deployment of an embarrassingly parallel application. In this paper, we describe the improvements in our deployment. We screened ZINC database against four targets implicated in malaria. During more than 2 months and a half, we have achieved 140 million dockings, representing an average throughput of almost 80,000 dockings per hour. This was made possible by the availability of thousands of CPUs through different infrastructures worldwide. Through the acquired experience, the WISDOM production environment is evolving to enable an easy and fault-tolerant deployment of biological tool

Grid enabled high throughput virtual screening against four different targets implicated in malaria

PCSVInternational audienceAfter having deployed a first data challenge on malaria and a second one on avian flu, respectively in summer 2005 and spring 2006, we are demonstrating here again how efficiently the computational grids can be used to produce massive docking data at a high-throughput. During more than 2 months and a half, we have achieved at least 140 million dockings, representing an average throughput of almost 80,000 dockings per hour. This was made possible by the availability of thousands of CPUs through different infrastructures worldwide. Through the acquired experience, the WISDOM production environment is evolving to enable an easy and fault-tolerant deployment of biological tools; in this case it is the FlexX commercial docking software which is used to dock the whole ZINC database against 4 different targets

Grid enabled virtual screening against malaria

34 pages, 5 figures, 3 tables, to appear in Journal of Grid Computing - PCSV, à paraître dans Journal of Grid ComputingWISDOM is an international initiative to enable a virtual screening pipeline on a grid infrastructure. Its first attempt was to deploy large scale in silico docking on a public grid infrastructure. Protein-ligand docking is about computing the binding energy of a protein target to a library of potential drugs using a scoring algorithm. Previous deployments were either limited to one cluster, to grids of clusters in the tightly protected environment of a pharmaceutical laboratory or to pervasive grids. The first large scale docking experiment ran on the EGEE grid production service from 11 July 2005 to 19 August 2005 against targets relevant to research on malaria and saw over 41 million compounds docked for the equivalent of 80 years of CPU time. Up to 1,700 computers were simultaneously used in 15 countries around the world. Issues related to the deployment and the monitoring of the in silico docking experiment as well as experience with grid operation and services are reported in the paper. The main problem encountered for such a large scale deployment was the grid infrastructure stability. Although the overall success rate was above 80%, a lot of monitoring and supervision was still required at the application level to resubmit the jobs that failed. But the experiment demonstrated how grid infrastructures have a tremendous capacity to mobilize very large CPU resources for well targeted goals during a significant period of time. This success leads to a second computing challenge targeting Avian Flu neuraminidase N1

Large Scale In Silico Screening on Grid Infrastructures

Large-scale grid infrastructures for in silico drug discovery open opportunities of particular interest to neglected and emerging diseases. In 2005 and 2006, we have been able to deploy large scale in silico docking within the framework of the WISDOM initiative against Malaria and Avian Flu requiring about 105 years of CPU on the EGEE, Auvergrid and TWGrid infrastructures. These achievements demonstrated the relevance of large-scale grid infrastructures for the virtual screening by molecular docking. This also allowed evaluating the performances of the grid infrastructures and to identify specific issues raised by large-scale deployment.Comment: 14 pages, 2 figures, 2 tables, The Third International Life Science Grid Workshop, LSGrid 2006, Yokohama, Japan, 13-14 october 2006, to appear in the proceeding

Nitrogen hydrides in the cold envelope of IRAS16293-2422

Nitrogen is the fifth most abundant element in the Universe, yet the gas-phase chemistry of N-bearing species remains poorly understood. Nitrogen hydrides are key molecules of nitrogen chemistry. Their abundance ratios place strong constraints on the production pathways and reaction rates of nitrogen-bearing molecules. We observed the class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI, covering most of the frequency range from 0.48 to 1.78~THz at high spectral resolution. The hyperfine structure of the amidogen radical o-NH2 is resolved and seen in absorption against the continuum of the protostar. Several transitions of ammonia from 1.2 to 1.8~THz are also seen in absorption. These lines trace the low-density envelope of the protostar. Column densities and abundances are estimated for each hydride. We find that NH:NH2:NH3=5:1:300. {Dark clouds chemical models predict steady-state abundances of NH2 and NH3 in reasonable agreement with the present observations, whilst that of NH is underpredicted by more than one order of magnitude, even using updated kinetic rates. Additional modelling of the nitrogen gas-phase chemistry in dark-cloud conditions is necessary before having recourse to heterogen processes

Virtual Screening on Large Scale Grids

PCSV, article in press in Parallel ComputingLarge scale grids for in silico drug discovery open opportunities of particular interest to neglected and emerging diseases. In 2005 and 2006, we have been able to deploy large scale virtual docking within the framework of the WISDOM initiative against malaria and avian influenza requiring about 100 years of CPU on the EGEE, Auvergrid and TWGrid infrastructures. These achievements demonstrated the relevance of large scale grids for the virtual screening by molecular docking. This also allowed evaluating the performances of the grid infrastructures and to identify specific issues raised by large scale deployment

The distribution of water in the high-mass star-forming region NGC 6334I

We present observations of twelve rotational transitions of H2O-16, H2O-18, and H2O-17 toward the massive star-forming region NGC 6334 I, carried out with Herschel/HIFI as part of the guaranteed time key program Chemical HErschel Surveys of Star forming regions (CHESS). We analyze these observations to obtain insights into physical processes in this region. We identify three main gas components (hot core, cold foreground, and outflow) in NGC 6334 I and derive the physical conditions in these components. The hot core, identified by the emission in highly excited lines, shows a high excitation temperature of 200 K, whereas water in the foreground component is predominantly in the ortho- and para- ground states. The abundance of water varies between 4 10^-5 (outflow) and 10^-8 (cold foreground gas). This variation is most likely due to the freeze-out of water molecules onto dust grains. The H2O-18/H2O-17 abundance ratio is 3.2, which is consistent with the O-18/O-17 ratio determined from CO isotopologues. The ortho/para ratio in water appears to be relatively low 1.6(1) in the cold, quiescent gas, but close to the equilibrium value of three in the warmer outflow material (2.5(0.8)).Comment: 7 pages, 3 figures, accepted by A&

The CHESS chemical Herschel surveys of star forming regions: Peering into the protostellar shock L1157-B1. I. Shock chemical complexity

We present the first results of the unbiased survey of the L1157-B1 bow shock, obtained with HIFI in the framework of the key program Chemical Herschel surveys of star forming regions (CHESS). The L1157 outflow is driven by a low-mass Class 0 protostar and is considered the prototype of the so-called chemically active outflows. The bright blue-shifted bow shock B1 is the ideal laboratory for studying the link between the hot (around 1000-2000 K) component traced by H2 IR-emission and the cold (around 10-20 K) swept-up material. The main aim is to trace the warm gas chemically enriched by the passage of a shock and to infer the excitation conditions in L1157-B1. A total of 27 lines are identified in the 555-636 GHz region, down to an average 3 sigma level of 30 mK. The emission is dominated by CO(5-4) and H2O(110-101) transitions, as discussed by Lefloch et al. (2010). Here we report on the identification of lines from NH3, H2CO, CH3OH, CS, HCN, and HCO+. The comparison between the profiles produced by molecules released from dust mantles (NH3, H2CO, CH3OH) and that of H2O is consistent with a scenario in which water is also formed in the gas-phase in high-temperature regions where sputtering or grain-grain collisions are not efficient. The high excitation range of the observed tracers allows us to infer, for the first time for these species, the existence of a warm (> 200 K) gas component coexisting in the B1 bow structure with the cold and hot gas detected from ground

First detection of ND in the solar-mass protostar IRAS16293-2422

In the past decade, much progress has been made in characterising the processes leading to the enhanced deuterium fractionation observed in the ISM and in particular in the cold, dense parts of star forming regions such as protostellar envelopes. Very high molecular D/H ratios have been found for saturated molecules and ions. However, little is known about the deuterium fractionation in radicals, even though simple radicals often represent an intermediate stage in the formation of more complex, saturated molecules. The imidogen radical NH is such an intermediate species for the ammonia synthesis in the gas phase. Herschel/HIFI represents a unique opportunity to study the deuteration and formation mechanisms of such species, which are not observable from the ground. We searched here for the deuterated radical ND in order to determine the deuterium fractionation of imidogen and constrain the deuteration mechanism of this species. We observed the solar-mass Class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI as part of the Herschel key programme CHESS (Chemical HErschel Surveys of Star forming regions). The deuterated form of the imidogen radical ND was detected and securely identified with 2 hyperfine component groups of its fundamental transition in absorption against the continuum background emitted from the nascent protostar. The 3 groups of hyperfine components of its hydrogenated counterpart NH were also detected in absorption. We derive a very high deuterium fractionation with an [ND]/[NH] ratio of between 30 and 100%. The deuterium fractionation of imidogen is of the same order of magnitude as that in other molecules, which suggests that an efficient deuterium fractionation mechanism is at play. We discuss two possible formation pathways for ND, by means of either the reaction of N+ with HD, or deuteron/proton exchange with NH.Comment: Accepted; To appear in A&A Herschel/HIFI Special Issu