Application of Cloud Computing Resources for Virtual Screening

描述（由申请人提供）：这是一个应用程序，用于开发可扩展的计算基础设施，以使用Amazon EC2云计算环境和自动对接工具对化学库进行虚拟筛选。基于结构的虚拟筛选是药物发现过程中的重要工具（1-7）。使用计算工具可以筛选大型化合物文库，以确定假定的配体-受体相互作用（8-9）。确定有效的靶点和治疗性化合物对公众健康和制药业的经济实力都具有长期的重要性。基于受体的虚拟筛选（VS）是一种利用计算工具将小分子量化合物锁定为蛋白质受体或酶的技术。该技术最常用于药物发现，其中一个大的化学结构库可以被对接和评分，以评估化合物与药物靶标结合的潜力。然而，高吞吐量虚拟筛选是计算密集型的，并且构建、维护和管理专用计算集群的成本限制了大型大学和商业企业对这些技术的访问。基于internet的计算（也称为云计算）是一种业务服务模型，其中计算资源可根据需要按需访问，并且价格合理、可扩展且安全。我们利用Amazon EC2云计算环境对100到10000种化合物的化学文库进行虚拟筛选，针对两个治疗感兴趣的靶点。该应用程序将进一步扩大虚拟筛选的能力，方法如下：(1)开发计算集群虚拟化和管理所需的软件基础设施；(2)开发用于提交和管理虚拟筛选请求和评估结果的基本用户界面；(3)通过与我们的合作者分析筛选结果来验证该方法。该平台的测试将集中在功能和实用性上：(1)展示筛选已知治疗靶点的140万至200万种化合物库的能力；(2)使用等效对接软件、化学库和目标，将性能与专用集群进行比较；(3)利用网络界面进行虚拟屏幕的能力。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.