"Expanding our current portal into a freely-available, full-service centre for drug discovery and optimization would be even more valuable than what currently exists", stated Stan Watowich, one of the portal originators and associate professor in the Department of Biochemistry & Molecular Biology at The University of Texas Medical Branch in Galveston.
The Watowich Laboratory and the Texas Advanced Computing Center (TACC) at the University of Texas at Austin have been collaborating on the portal since 2013. Steve Mock, a portal developer, and John Fonner, a life sciences researcher worked directly with Watowich and his team to redevelop the portal. They did this on top of TACC's Agave Science-as-a-Service (SCaaS) platform to be more user friendly and to take advantage of the Lonestar 4 high performance supercomputer.
"With TACC's help, the user experience instantly became more robust, easier to negotiate, and much quicker to get your job submitted and completed", Stan Watowich stated.
Making a new therapeutic drug available to those who need it is a long process that ends with extensive clinical trials, according to Fonner. Getting to clinical trials, however, is dependent on finding and optimizing an effective drug candidate that binds strongly to the relevant biological target.
"The drug discovery portal lets researchers start with the biological target that is important to them and computationally test out hundreds of thousands of potential drug candidates using the physics of molecular interactions to find the best ones. From there, it is up to the researcher to pick which candidates to further optimize and test experimentally", he stated.
John Fonner continued: "By increasing the visual and analytics capabilities of the site, researchers will be able to explore their results through an interactive platform that can very quickly convey important binding information, allowing them to make decisions on which promising compounds to study further."
User data will move to Lonestar 5 in late 2015 and researchers will experience more power, speed, and overall capability. With 50 percent more cores than Lonestar4 and about four times the performance, users will get their drug discovery calculations done that much quicker. The new Cray XC40 supercomputer, which contains more than 30,000 Intel Xeon processing cores from the E5-2600 v3 product family, will provide a peak performance of 1.25 petaflops, and TACC expects the system to be in high demand.
"It's immensely satisfying to be a part of developing a tool that puts the complexity of the drug screening workflow and the power of TACC's supercomputers into the hands of researchers looking to help combat disease", Steve Mock stated. "This simple web interface democratizes access to a drug discovery pipeline previously unavailable to most people."
In terms of overall impact on research, this next level of supercomputing power will offer larger libraries for users to screen, and provide them with a larger chemical space to find possible drug candidates - "it's where the next level in the science will go", Stan Watowich stated.
The DrugDiscovery@TACC portal is not limited by geographic boundaries. In the Unites States and Europe, the portal provides researchers access to supercomputer resources to help them launch a drug discovery project with little effort - a point and click model. Researchers don't have to become a computational chemists themselves. They can take their disease target of interest and overnight obtain possible drug candidates, bring the computer predictions into the lab and test them doing the predictive work quickly.
The DrugDiscovery portal is also beneficial to researchers in developing countries that do not have access to high performance computing. All they need is a web browser and they can perform the same sophisticated calculations with the same supercomputer power that anyone in the developed world has at their fingertips. "In many cases, they would have large difficulties even conceiving doing this work", Stan Watowich stated. "We have researchers from a number of countries including Colombia, Cuba, Venezuela, and several countries in Africa. The portal has allowed them to start competing with research in the developed world."
After attending a workshop taught by Stan Watowich in 2014 in Medellin, Colombia, Carolina Quintero Gil of the Universidad Nacional received access to the portal. She stated: "Being able to participate in the course and having access to the portal helped me advance my research. I found commercial candidates to potently inhibit the Hepatitis E virus infection, a viral model of great importance in Colombia. Access to TACC resources saved me a lot of time and soon I will be able to start the in vitro evaluation of compounds found through the portal docking tool."
Stan Watowich, Steve Mock and John Fonner have many goals for the portal. One is to interface with IBM's World Community Grid (WCG), which has two million individual computers available for simulations and will add software to do more advanced molecular dynamic calculations to give more accurate predictions.
In addition, the team foresees developing and implementing software for generating new libraries and making visualizations available for researchers to download.
Finally, there's an additional component to integrate synthetic chemists into the mix. Once a researcher has a drug lead that works in the lab and in an animal model, it is important to bring it to the high value' compound state, which means it is now a candidate for commercialization. "This is another component of the centre, which would be non-computational, but would leverage the computational prediction", Stan Watowich stated.
Portal user Jay Groppe, associate professor at the Texas A&M University Baylor College of Dentistry, summed up the value of the DrugDiscovery@TACC portal: "Without any previous experience in drug development, the way forward was unclear. An in silico screen could be conducted either commercially for tens of thousands of dollars, or after purchase of a software license and investment of significant time and effort learning routines of a suite of docking programmes."
Jay Groppe continued: "Through a tremendously opportune stroke of luck, the portal at TACC came to my attention and within days I was analyzing a long list of tantalizing dockings from the large 642,000+ drug-like compound library that eventually lead to the identification of novel allosteric inhibitors. As a result, a provisional patent has been filed, a seed-grant awarded and a solid NIH R01 proposal submitted. All without any experience or expense, yet with ready and willing support from TACC and UTMB. This is a remarkable resource and more scientists will realize this readily available asset at their disposal. I have enjoyed what is essentially a personal supercomputer for drug screening that rivals and likely surpasses any accessible to the large pharmaceutical concerns."