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The key role of the UNICORE technology in european distributed computing infrastructures supporting e-science applications in the decades to come
Abstract
Computational simulations and thus scientific computing is the third pillar alongside theory and experiment in science for a few decades now. In the last decade, the term Grid and later e-science evolved as a new research field that both focus on collaboration in key areas of science using so-called next generation distributed computing infrastructures (DCIs) to extend the potential of scientific computing. During the past years, significant international and broader interdisciplinary e-research is increasingly carried out by global collaborations that often share the resources of these DCIs. Examples of these DCIs have been the Enabling Grid for e-Science (EGEE) infrastructure as well as the Distributed European Infrastructure for Supercomputing Applications (DEISA) in Europe. Despite of the early success we can observe a change in the near future with these infrastructures since these project-based funded infrastructures like EGEE or DEISA move towards a more sustainable funding model in Europe. The result is a different landscape of DCIs as experienced in the last decade leading to the European Grid Initiative (EGI) infrastructure and the Partnership for Advanced Computing in Europe (PRACE) infrastructure. At the same time end-user communities organized themselves better than before and developed roadmaps for their scientific endeavours. In this context, the European Strategy Forum on Research Infrastructures (ESFRI) released an interesting roadmap of 44 projects that bear the potential of a high amount of end-users that also require DCIs for their scientific e-research. Another promising roadmap alignment of DCI end-users can be observed in the context of the Virtual Physiological Human (VPH) to push and focus efforts related to e-Health. In parallel to all the aforementioned 'emerging changes' UNICORE is still established as the technology of choice for resources used in High Performance Computing (HPC). The question remains whether this will be the case in the future and to which extend new e-research endeavours will influence the funding opportunities (and thus major developments) for the UNICORE community. This contribution will give some answers to these questions by providing one potential UNICORE roadmap that reveals a promising future.
International e-Infrastructures offer a wide variety of Information and Communications Technology (ICT) services that federate computing, storage, networking and other hardware in order to create an 'innovative toolset' for multidisciplinary research and engineering. UNICORE services are known to be secure, reliable, and fast providing researchers all over the world with powerful software that enables the use of those e-Infrastructures as a 'commodity tool' in daily geographically distributed activities. As key technology provider of the European Grid Infrastructure (EGI), UNICORE is available as part of the Unified Middleware Distribution (UMD) serving the needs of researchers that require mainly High Throughput Computing (HTC). On the other end of the scale, UNICORE offers specifically optimized resources within the Partnership for Advanced Computing in Europe (PRACE) today. Beyond Europe, UNICORE installations are emerging more and more such as within the Extreme Science and Engineering Discovery Environment (XSEDE) US multi-disciplinary e-Infrastructure (aka Cyberinfrastructure) offering both HTC and HPC resources. The grand challenges in science, engineering, and in society that need to be solved towards 2020 and beyond will increasingly require both geographical and intellectual collaboration across multiple disciplines. International e-Infrastructures are considered to be one key toolset to tackle those grand challenges and this contribution will outline several options how UNICORE can remain one 'technology of choice' towards 2020. A strategic roadmap is presented that illustrates the role of UNICORE alongside the European Commission's (EC) vision for Europe in 2020, including the opportunities that arise for UNICORE in the context of the Digital Agenda for Europe. The roadmap also includes how UNICORE can play a role to tackle, or perhaps rather contribute with processing to the avoidance of 'big data waves' arising from a wide variety of e-Infrastructure users emerging from the European Strategy Forum on Research Infrastructures (ESFRIs).
Background:
Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery.
Motivation:
Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR), and on a new promising one, glutathione-S-transferase.
Methods:
In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures.
Results:
On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed.
Conclusion:
The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software on computational grids in finding hits against three different targets (PfGST, PfDHFR, PvDHFR (wild type and mutant forms) implicated in malaria. Grid-enabled virtual screening approach is proposed to produce focus compound libraries for other biological targets relevant to fight the infectious diseases of the developing world.