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以及 新的生物活性化合物的发现和开发。特别是，虚拟筛选现在被广泛用于 发现结合和抑制药用靶标的新化合物。AutoDock程序套件是 目前使用最广泛的、可免费获得的自动计算对接方法。这一成功是 在前一批准期内开展的工作的几个方面的成果： 开发解决社区中感兴趣的问题的方法，如共价对接和 活动站点预测，以及用户友好界面和用户支持的开发，以确保 方法可供尽可能广泛的社区访问。作为这项工作的结果，我们已经看到了采用和 由专家用户扩展AutoDock套件，使用该套件作为计算研究的平台 化学和算法开发，与实验化学家和 不是计算化学专家的分子生物学家。在拟议的工作中，我们将发展 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，以满足大型用户社区不断扩大和多样化的需求。我们将开发新的 用于配体设计的方法，允许产生新的化合物，采用特定的限制条件，将 确保这些化合物是可人工合成的，并预计具有理想的药理作用。 属性。我们还将继续并扩大我们对用户支持的坚定承诺，创建 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.