AutoDock Suite: Next Generation Environment for Drug Design

项目摘要 计算对接是分析生物分子结构和功能的重要工具， 发现和开发新的生物活性化合物。特别地，虚拟筛选现在被广泛用于 发现新的化合物来结合和抑制医学目标。AutoDock程序套件是 目前最广泛使用的、免费可用的自动计算对接方法。这一成功是 在上一个赠款期内开展的工作的几个方面的结果： 开发方法来解决社区感兴趣的问题，例如共价对接， 活动网站预测，并开发用户友好的界面和用户支持，以确保 方法可以被尽可能广泛的社区使用。由于这项工作，我们看到了采用和 专家用户对AutoDock套件的扩展，使用该套件作为计算研究的平台 化学和算法开发，与实验化学家的广泛应用并行， 不是计算化学专家的分子生物学家。在拟议的工作中，我们将开发 AutoDock成为下一代药物设计和发现工具。这将包括方法的扩展 的AutoDock，以满足不断扩大和多样化的需求，一个庞大的用户社区。发展新型 用于配体设计的方法，其允许产生新的化合物，采用特定的限制， 确保这些化合物是合成可及的，并且预测具有期望的药理学活性。 特性.我们还将继续并扩大我们对用户支持的坚定承诺， 简化用户社区对AutoDock套件的使用，并提供有效的支持和培训。

Project Summary Computational docking is an essential tool for analysis of biomolecular structure and function and for the discovery and development of new bioactive compounds. In particular, virtual screening is now widely used to discover new compounds to bind and inhibit targets of medicinal interest. The AutoDock Suite of programs is currently the most widely used, freely-available method for automated computational docking. This success is the result of several aspects of the work performed under the previous granting period: the continued development of the method to address problems of interest in the community, such as covalent docking and active site prediction, and the development of user-friendly interfaces and user support that ensure that the method is accessible to the widest community possible. As a result of this work, we have seen adoption and extension of the AutoDock suite by expert users, using the suite as a platform for research in computational chemistry and algorithm development, in parallel with widespread application by experimental chemists and molecular biologists who are not experts in computational chemistry. In the proposed work, we will develop AutoDock into a next generation tool for drug design and discovery. This will include extensions of the methods of AutoDock to address the expanding and varied needs of a large user community. We will develop new methods for ligand design that allow to generate novel compounds, employing specific constraints that will ensure that such compounds are synthetically accessible, and predicted to have desirable pharmacological properties. We will also continue and expand our strong commitment to user support, creating interfaces that streamline use of the AutoDock suite by the user community, and providing effective support and training.