The Discovering Dengue Drugs - Together Scientist have provided an update on the Discovering Dengue Drugs – Together project, which was included in the June, 2009 Newsletter. You may review the newsletter online here, or for your convenience the update is as follows:

Discovering Dengue Drugs – Together, University of Texas Medical Branch, Galveston, Texas, USA and the University of Chicago, Chicago, Illinois, USA
We are back on track with our Discovering Dengue Drugs - Together project, and life is returning to some semblance of normalcy in Galveston and at UTMB. We thank World Community Grid members for their support and patience during the past 6 months following Hurricane Ike.

Phase 1 of our project is now complete! We have screened (i.e. computationally tested) more than 3 million potential drug candidates against each of 10 different proteases from dengue, West Nile, and hepatitis C viruses. Compounds that inhibit these target proteases will prevent virus replication. We continue to analyze the 30 million Phase 1 results, although several compounds tested in the laboratory have already shown excellent activity in our biochemical and cell-based assays. These compounds will be further characterized and tested for in vivo antiviral activity.

Phase 2 of our project is being optimized at Texas Advanced Computer Center (TACC; www.tacc.utexas.edu) in Austin, Texas and ported by IBM to the grid for testing. This phase will perform extensive molecular dynamics calculations to accurately calculate binding free energies for the best potential drug candidates predicted in Aim 1. These calculations will significantly reduce the number of false positive predictions produced in Phase 1, thereby increasing our success rate for identifying experimentally active compounds from ~10% to >80%. Launch of Phase 2 is anticipated for early summer, 2009.

As we prepare to launch Phase 2 of our quest to discover drugs for dengue, west Nile, and hepatitis C infections, we will continue Phase 1 calculations, this time in support of a collaborative drug discovery effort to treat the disease leishmaniasis. This work is done in partnership with researchers from Universidad de Antioquia, Colombia ( http://www.pecet-colombia.org ). Leishmania affects about 12 million people throughout the tropics, subtropics, and southern Europe, with about 2 million new cases each year. The disease is spread by the bite of sand flies infected the Leishmania parasite. Although a handful of antimicrobials exist to treat some forms of leishmaniasis, concerns about their modes of delivery, effectiveness, resistance, and cost spur our drug discovery efforts into novel anti-Leishmania drugs. For this project, scientists in Colombia identified a set of enzymes critical for survival of the Leishmania parasite. Atomic structures exist for each of these enzymes, this allowing us to computationally examine our drug candidate library for compounds that prevent the Leishmania enzymes from functioning.

As reported earlier, this project is now running better than ever before. We have moved our main computational tasks (those required to prepare work units for World Community Grid and analyze results returned from the grid) to the supercomputers housed at TACC. This establishes a nice synergy between one of the world's most powerful supercomputers and the world's largest computer grid. Our storage capabilities have increased in size and robustness with redundant storage occurring at TACC and locally on our 12 TByte IBM DS3200 disk system.

As stated before, we greatly appreciate the computer time that has been unselfishly provided by the members of World Community Grid!