A WEB-BASED AUTOMATIC MOLECULAR DOCKING SYSTEM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管众所周知的算法缺陷，分子对接屏幕在最近几年取得了重要的成功。像其他筛选技术一样，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强调使假阳性变得廉价。对接是目前最实用的利用结构发现配体的技术。不幸的是，进入壁垒在很大程度上限制了这项技术对专家及其合作者的使用。对接数据库的获取成本很高，需要相当大的操作，而且软件也很复杂。这降低了这项技术的影响，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，将对接带给广泛的受众，并允许将其应用于新的问题。第一个目标是本着BLAST的精神，开发受过教育的非专家可以通过基于网络的应用程序使用的数据库和工具。诚然，这种以目标为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：我们使用对接筛选结果来研究指纹结合位点的识别和潜在功能。

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.