Project summary Automated docking is a computational method that is now routinely used for identifying small molecules that have the potential to be new drugs. Over the past three decades we have developed docking methods and our docking software AutoDock is not the most cited docking software with over 40,000 citations in the peer reviewed literature. As such, it has become an important resource for the community. We seek to create a national resource that will allow us to maintain and modernize this software to adapt to evolving hardware platforms and operating systems, to keep the software up to date and relevant by incorporating the latest algorithmic developments, and to support its large user community. In parallel with these efforts, an important goal of the proposed Resource is to chart a path toward a self-sustained software ecosystem where contributors from around the world will contribute to maintain and further develop this software after the lifetime of this award. This goal has been achieved by other successful open source projects such as Debian and Python, and the written interest of many colleagues bolster our confidence that the AutoDock software too can reach this goal. To this end we propose three specific aims. Our first aim is to maintain and modernize the software code. This critical work is needed for the software to remain functional and able to address the evolving needs of the community. As we overhaul the software, we will leverage newer toolkits for generating modern and intuitive graphical user interfaces. These interfaces enable researchers, such as clinical physicians or chemists with limited computational skills for instance, to use docking to better understand the mechanism of action of a drug and optimize it. Our second aim is concerned with making our software tools interoperable with other important modeling software tools such as molecular dynamics for instance. Not only does this augment the potential of docking to lead to novel therapeutic molecules, but it also serves our goal to create a community of developers who will ultimately maintain this software ecosystem. Finally our third and final aim is about supporting the large user community, growing it and ensuring that the software is easily discovered, obtained and installed. We have a long track record of developing open source software promoting best practices in software engineering, and making these tools usable, useful, and available to the community. Likewise we have supported and grown our user community for many years. This puts us in a unique position to create the proposed research which, if funded, will allow us to convert this valuable software code into a community supported software ecosystem ensuring that this software will continue to support the design of novel therapeutic molecules beyond the lifetime of this award.

Project Narrative Automated docking has become a widely used technique for structure based rational drug design, and AutoDock, the most cited docking software tool with a large user base, is a key resource for the rationalization or design, and optimization of drug receptor interactions. Keeping this software running on evolving hardware and operating systems requires maintenance. We propose the creation of a national resource to maintain and modernize the software, for supporting the growth of a community of open source developers towards a self-sustained software resource, and for augmenting our user training efforts.