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August 21, 2007 update
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Phase 1 (Autodock) of this project was launched August 21,
2007.
January 22, 2008 update
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An initial optimization of docking parameters was completed in
early Fall, 2007. This allowed us to reduce computation time ~20-fold
without impacting the accuracy of pose predications.
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Dengue virus NS3 protease (Protein Data Bank entry 2FOM) was
used as a target to screen a combined drug and lead-like library containing
2.2 million compounds. These calculations (termed workgroup 0201) were
completed in ~2 months. Grid resources for these calculations were limited
to <10% of World Community Grid to minimize file transfer bottlenecks
resulting from packing only a single ligand into each workunit.
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Predicted inhibitors obtained from screening our ligand
library against dengue virus NS3 protease are being analyzed in our
laboratory using a protease inhibition assay. Compounds with promising
inhibition constants will be further evaluated in cell culture and animal
models.
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West Nile virus NS3 protease (Protein Data Bank entry 2FP7)
was used as a target to screen a combined drug and lead-like library
containing 2.2 million compounds. These calculations (termed workgroup 0301)
were completed in ~2 months and ended in early January ‘08. Grid resources
for these calculations were also limited to <10% of World Community Grid to
minimize file transfer bottlenecks resulting from packing only a single
ligand into each workunit.
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Predicted inhibitors obtained from screening our ligand
library against West Nile virus NS3 protease are being analyzed in our
laboratory using a protease inhibition assay. Compounds with promising
inhibition constants will be further evaluated in cell culture and animal
models.
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Additional docking calculation optimizations are entering beta
testing. These optimizations will enable us to reach our goal of screening
our ligand library against a single protein in less than 2 weeks. This
involves packaging multiple ligands (~10) into a single workunit, thereby
minimizing file transfer bottlenecks. In addition, checksum error checking
will be embedded within each workunit, eliminating the use of redundant
calculations to validate each workunit.
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Trypsin protease (Protein Data Bank entry 1EB2) is being
screened against our ligand library to provide a negative control for
inhibitor discovery (termed workgroup 0401).
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Hepatitis C virus protease is being readied for computational
screening.
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Our Discovering Dengue Drugs – Together project has currently
benefited from 3,626 years of computer processing time on World Community
Grid. We are grateful to those individuals who have unselfishly volunteered
their computers to help us find cures for dengue, West Nile, and Hepatitis C
diseases.
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