R24GM145962

Resource for Structure-Based Computational Drug Discovery and Design (RSD3) - 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 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 bolsters 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.

Scripps Research Institute

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

La Jolla, California 920371000 United States

Single Zip Code

Limited Competition: NIGMS National and Regional Resources (R24 - Clinical Trial Not Allowed) (PAR-19-301)

Amendment Since initial award the total obligations have increased 268% from $1,159,874 to $4,271,005.