This is a Phase II application for continued development of the Chemalytics Platform, a scalable computational infrastructure to enable virtual screening of chemical libraries using the Amazon EC2 cloud computing environment and automated docking tools. Structure-based virtual screening is an important tool in the drug discovery process (1-7). The use of computational tools has allowed for the screening of large libraries of chemical compounds to identify putative ligand-receptor interactions (8-9). The identification of valid targets and therapeutic compounds has long-term importance both to the public health and the economic strength of the pharmaceutical industry. Receptor-based virtual screening (VS) is a technique in which computational tools are used dock small molecular weight compounds into a protein receptor or enzyme. This technique is most often used in drug discovery, where a large library of chemical structure can be docked and scored to assess the potential if a compound to bind to a drug target. However, high-throughput virtual screening is computationally intensive, and the cost of building, maintaining, and managing a dedicated computing cluster limits access to these technologies to large universities and commercial enterprises. Internet-based computing, also known as cloud computing, is a business service model in which computational resources are accessed on-demand as needed, and is affordable, scalable, and secure. We have completed the Phase I goals of a building a web-based interface to manage users, jobs, and display results from virtual docking screens. The current system employs the Amazon EC2 environment and has been successfully used to screen chemical libraries of more than 2.3 million structures in an economical and rapid fashion. In collaboration with a biotechnology partner, we are now pursuing chemical leads which are active against prostate cancer cell lines. In this phase we will expand the capabilities of the current system through the following technical achievements: (1) integration of additional chemical libraries and library filtering tools to focus search space prior to docking; (2) enhancement of end user ability to evaluate results through integration of data analysis and visualization tools; (3) validation of this approach through analysis of screening results with our collaborators and commercial partners.