This is an application to develop 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 utilized the Amazon EC2 cloud computing environment for virtual screening of chemical libraries of 100 to 10000 compounds against two targets of therapeutic interest. This application will further expand the capacity for virtual screening by: (1) development of the software infrastructure required for computational cluster virtualization and management;(2) development of a basic user interface for submission and management of virtual screening requests and evaluation of results;(3) validation of this approach through analysis of screening results with our collaborators. The test of this platform will be focused on function and utility: (1) demonstrate the ability to screen a library of 1.4 million to 2.0 million compounds against known therapeutic targets;(2) comparison of performance against a dedicated cluster using equivalent docking software, chemical libraries, and targets;(3) ability to utilize the web interface to conduct virtual screens.
The Phase I SBIR project """"""""Application of Cloud Computing Resources for Virtual Screening"""""""" will deliver new technologies for the structure-based identification of small molecule ligands of proteins and enzymes. By significantly increasing the ability of researchers to access tools for in-silico screening, we will facilitate identification of novel therapeutic compounds used in the treatment of disease, and thereby improving the public health.
