Advancing drug formulation: Insights from Dr. Julio Facelli
Dr. Julio Facelli began his career in Physics in Argentina and later conducted post-doctoral research at the University of Arizona. He is currently at the University of Utah. From 1995 to 2013, he served as the Director of the Center for High-Performance Computing, and he currently holds the positions of Distinguished Professor, and Vice Chair for Faculty, in the Department of Biomedical Informatics. He is also the Associate Director for Biomedical Informatics at the Utah Clinical and Translational Science Institute, Adjunct Professor of Nursing, Chemistry, and Physics, and a member of the Utah Nano Science Institute.
Dr. Facelli has been a pioneer in crystal structure prediction and its relevance to pharmaceutical development at the University of Utah. His research focuses on addressing critical challenges in drug formulation, particularly stability and concentration issues that often impede the practical use of potentially effective drugs. His team is working to predict crystal structures from first principles, thereby significantly enhancing the reliability and applicability of these predictions, utilizing advanced computational methods and leveraging the resources of the Open Science Grid (OSG), a partner of Computing for Humanity.
Advancing drug formulation
Dr. Facelli explains the importance of drug stability and the challenges posed by polymorphisms, which can affect the concentration and availability of drugs. Traditional methods using empirical potentials, although useful, require extensive parameter fitting. Dr. Facelli’s approach focuses on predicting crystal structures using first principles, which, while initially demonstrated on simpler compounds like glycine, aims to be extended to more complex pharmaceutical molecules. “We were able to do that only on glycine which it will be very difficult to convince people that that's a real drug. So, we are trying to go too much larger”, he explains.
The role of the High-Performance Computing Resources
A key aspect of Dr. Facelli's work is the use of the Open Science Grid (OSG), a powerful computational resource that distributes tasks across a very large distributed set of nodes, enabling large-scale calculations, with which Computing for Humanity is a partner. By adapting their algorithms to fit the OSG architecture, his team can conduct extensive computations that would otherwise be infeasible. This adaptation involved developing a steady-state genetic algorithm, allowing continuous evolution of the population and easy parallelization. “We make an effort to adapt our system to run the OSG and there is a paper* that is under review describing the method; and the advantage of the OSG is that you get huge of resources and essentially the way that we are running this”, he says.
Expanding Research Horizons
While the primary focus is on pharmaceutical applications, Dr. Facelli’s team also explores other areas, such as explosive formulations and autoimmune diseases triggered by infections. “But we are using our own in-house resources for that”, he expresses. The versatility of their methods demonstrates the broad applicability of their computational approaches.
Overcoming Challenges in Research
Reflecting on the broader research landscape, Dr. Facelli emphasizes the critical role of resources like the OSG, which provide unparalleled computational power. Without such resources, many complex problems would remain un tractable. He also highlights the importance of funding and the challenges faced by junior researchers in securing financial support, particularly in the current climate of reduced research funding. “I think that (another factor) that will discourage young people is the anti-science movement particularly exacerbated during the pandemic, all these crazy ideas about vaccines and things like that”.
Mentoring the Next Generation
Dr. Facelli finds great satisfaction in mentoring young scientists, helping them navigate the complexities of research and secure early-career funding. His dedication to fostering new talent underscores the collaborative spirit essential for scientific advancement. “Curiosity and dedication and understanding that research is somehow different because you need to accept failure as a common” he expresses. “If you don't fail often, you probably are not at the edge of the research and you need to live with that. You need to have ideas. But it's a lot of hard work”.
Final Thoughts
For researchers looking to utilize resources like the OSG and support from initiatives like Computing for Humanity, Dr. Facelli advises being prepared to adapt their methods to these unique architectures. While not every problem can be addressed with distributed computing, the potential benefits for suitable projects are immense.
* This is a preprint article; the final citation will be updated upon publication.