The Rothberg Institute for Childhood Diseases (TRI), a non-profit research institute devoted to discovering drugs for orphan childhood diseases such as Tuberous Sclerosis Complex (TSC), has released Version 2.0 of the Drug Design and Optimization Laboratory (D2OL) Software developed at Sengent, Inc. D2OL is based on Sengent's CommunityOS, a grid computing program that harnesses idle time on volunteer computers from the online community to create a "supercomputer". This system is capable of using chemical docking algorithms and statistical models to rapidly test potential drugs to cure orphan childhood diseases and fight emerging pathogens. D2OL Version 2.0 was designed for increased stability and reliability of the client-server system, improved client-server communications, decreased bandwidth requirements, and increased user capacity. Additionally, D2OL Version 2.0 will allow continued upgrades to the software without disrupting client usage. TRI supports two projects that utilize D2OL: the Bio-terrorism/Emerging Pathogens project that runs on 51,297 computers in 93 countries; and the CommunityTSC project that runs on 17,160 computers in 58 countries. Growth spurts experienced after the addition of SARS targets to the Bio- terrorism/emerging pathogens project prompted the development of a system which can accommodate in excess of a million users worldwide. The new software will be available for download by users of both projects on Thursday September 18th 2003. The purpose of the Bio-terrorism/Emerging Pathogens project is to target critical proteins of disease-causing microbes, such as SARS and anthrax, for virtual compound screening. The CommunityTSC project uses TSC-relevant proteins identified by sponsored collaborators at Harvard, Yale, and Fox Chase Cancer Center as drug targets for computational screening. The targets are screened against all commercially available drug-like chemical entities (an estimated 2.5 million potential drugs) to prioritize the compounds to be tested in the laboratory both at TRI and collaborating academic institutions worldwide. Since the start of this project, the first drug trial specifically designed to help children with TSC was initiated. We hope that this drug will serve as a model for testing drugs derived from the efforts of those engaged in the Community TSC project. Version 2.0 was designed with the user in mind. For eighteen months the support staff at TRI has collected and compiled a wish list from users and took the most frequently requested features and incorporated them into the new version. The new version is more robust and gives the users greater control over the communication with the servers located at TRI. The most frequent request was an increased number of work units for the power-users in the community. We are pleased to announce that the maximum number of work units has increased twenty fold to satisfy even the fastest nodes on our network. The Drug Design and Optimization Lab was established in November of 2001 to expedite and lower the cost of identifying drugs capable of addressing general health issues. The software was first applied to targets of potential bio-warfare/terrorism agents, specifically, to druggable targets of the SARS Virus in May of 2003. TRI first applied D2OL to find a cure for TSC in April of 2002. The latest Version of D2OL used in the fight against TSC is available at: www.childhooddiseases.org.