A Web-Based Automatic Molecular Docking System

基于网络的自动分子对接系统

• 批准号: 7173534
• 负责人: Brian K Shoichet
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173534
• 关键词: Internet; automated data processing; binding sites; bioengineering /biomedical engineering; chemical models; computational biology; computer simulation; computer system design /evaluation; high throughput technology; intermolecular interaction; ligands; molecular biology information system

DESCRIPTION (provided by applicant): Notwithstanding well-known algorithmic weaknesses, molecular docking screens have had important successes in recent years, and are now the most practical technique to leverage structure for ligand discovery. Unfortunately, barriers to entry have largely restricted the techniques to experts and their collaborators. Docking databases are expensive to acquire, require considerable manipulation, and the software is byzantine. This has diminished the impact of the technique and limited the sorts of problems to which it can be applied. We propose to develop tools and databases that will bring docking to a broad audience, in the spirit of BLAST, and allow its application to new questions. The specific aims are; Aim 1. To build a public docking service as a research tool. 1. Develop public databases suitable for docking: a. A database of 500,000 commercially available, "drug-like" compounds, b. A database of annotated metabolites. 2. Develop an interface to allow non-experts to screen these databases against target structures. 3. Develop scripts to completely automate the docking procedure. 4. Develop a computational platform to distribute the calculations. Aim 2. To create web-based analysis tools including a database of top scoring ligands. 1. Develop automated, interactive, visually rich and intuitive tools to analyze docking results: a. A results browser to facilitate prioritizing top scoring hits for purchasing and testing, b. Links to molecular graphics viewers to examine docked poses, c. Enrichment plots to illustrate the degree to which lists of known ligands score well, d. High level summaries, digests and statistics of docking calculations required for monitoring and diagnosing thousands of high-throughput automatic calculations. 2. Develop a database of top scoring docked ligands for over 1000 protein binding sites of both known and unknown function. Make this database available on the web. 3. Develop web-based tools to compare top scoring hit lists between pairs of binding sites. Extensive preliminary results suggest that these aims are feasible.

描述（由申请人提供）：尽管存在众所周知的算法弱点，但近年来分子对接筛选已取得重要成功，并且现在是利用结构进行配体发现的最实用技术。不幸的是，进入壁垒在很大程度上限制了专家及其合作者的技术。对接数据库的获取成本很高，需要大量的操作，而且软件是拜占庭式的。这削弱了该技术的影响，并限制了它可以应用于的问题的种类。我们建议开发工具和数据库，将对接到一个广泛的受众，在BLAST的精神，并允许其应用到新的问题。具体目标是：目标1。建设公共对接服务作为研究工具。1.开发适合对接的公共数据库：500，000种市售“药物样”化合物的数据库，B.注释代谢物的数据库。2.开发一个界面，允许非专家根据目标结构筛选这些数据库。3.开发脚本以完全自动化对接过程。4.开发一个计算平台来分发计算结果。目标2.创建基于网络的分析工具，包括得分最高的配体数据库。1.开发自动化、交互式、视觉丰富和直观的工具来分析对接结果：a.结果浏览器，用于促进对用于购买和测试的最高得分命中进行优先化，B.链接到分子图形查看器检查停靠姿态，c。富集图说明已知配体列表得分良好的程度，d。对接计算的高级摘要、图表和统计数据，用于监控和诊断数千个高通量自动计算。2.为超过1000个已知和未知功能的蛋白质结合位点开发一个得分最高的对接配体数据库。将此数据库放在网上。3.开发基于网络的工具来比较成对结合位点之间的最高得分命中列表。广泛的初步结果表明，这些目标是可行的。