A WEB-BASED AUTOMATIC MOLECULAR DOCKING SYSTEM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尽管众所周知的算法的弱点，分子对接屏幕有重要的成功，在最近几年。与其他筛选技术一样，其目标是发现新的配体。假阴性是可以容忍的，而对筛选可用化合物的重视使假阳性变得便宜。对接现在是利用结构进行配体发现的最实用的技术。不幸的是，进入障碍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，将对接到广泛的受众，并允许其应用到新的问题。第一个目标是开发数据库和工具，受过教育的非专家可以通过基于Web的应用程序使用，在BLAST的精神。这一公认的目标导向的目标将提供一种能够产生很大影响的技术。第二个目标是假设驱动：我们研究使用对接筛选结果指纹结合位点的识别和潜在的功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Notwithstanding well-known algorithmic weaknesses, molecular docking screens have had important successes in recent years. Like other screening techniques, the goal is to discover novel ligands. False negatives are tolerated, and the emphasis on screening available compounds makes false positives cheap. Docking is now the most practical technique to leverage structure for ligand discovery. Unfortunately, barriers to entry have largely restricted the technique 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, and allow its application to new questions. The first aim is to develop databases and tools that an educated non-expert can use via a web-based application, in the spirit of BLAST. This admittedly goal-oriented aim would provide an enabling technology that would have much impact. The second aim is hypothesis driven: we investigate using docking screening results to fingerprint binding sites for recognition and potentially function.