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‘Alexa for chemistry’: National Science Foundation puts VCU and partners on fast track to build open network

Oct 31, 2019

4 min

D. Tyler McQuade, Ph.D., professor in the Department of Chemical and Life Science Engineering at Virginia Commonwealth University College of Engineering, is principal investigator of a multi-university project seeking to use artificial intelligence to help scientists come up with the perfect molecule for everything from a better shampoo to coatings on advanced microchips.


The project is one of the first in the U.S. to be selected for $994,433 in funding as part of a new pilot project of the National Science Foundation (NSF) called the Convergence Accelerator (C-Accel). McQuade and his collaborators will pitch their prototype in March 2020 in a bid for additional funding of up to $5 million over five years.


Adam Luxon, a Ph.D. student in the Department of Chemical and Life Science Engineering who has been involved from the beginning, explained it this way: “We want to essentially make the Alexa of chemistry.”


Just as Amazon, Google and Netflix use data algorithms to suggest customized predictions, the team plans to build a platform and open knowledge network that can combine and help users make sense of molecular sciences data pulled from a wide range of sources including academia, industry and government.

The idea is right in line with the goal of the NSF program: to speed up the transition of convergence research into practice in nationally critical areas such as “Harnessing the Data Revolution.”


The team itself reflects expertise across several specialties. Working with McQuade are James K. Ferri, Ph.D., professor in the Department of Chemical and Life Science Engineering; Carol A. Parish, Ph.D., professor of chemistry and the Floyd D. and Elisabeth S. Gottwald Chair in the Department of Chemistry at the University of Richmond; and Adrian E. Roitberg, Ph.D., professor in the Department of Chemistry at University of Florida. Two companies are also involved with the project: Two Six Labs, based in Arlington, Virginia, and Fathom Information Design, based in Boston, Massachusetts.


Currently, there is no shared network or central portal where molecular scientists and engineers can harness artificial intelligence and data science tools to build models to support their needs.


What’s more, while scientists have been able to depict what elements make up a molecule, how the atoms are arranged in space and what the properties of that molecule are (such as its melting point), there is no standard way to represent — or predict — molecular performance.


The team aims to fill these gaps by advancing the concept of a “molecular imprint.” The collaborators will create a new system that represents molecules by combining line-drawing, geometry and quantum chemical calculations into a single, machine-learnable format.


They will develop a central platform for collecting data, creating these molecular imprints and developing algorithms for mining the data, and will develop machine learning tools to create performance prediction models.


Parish said, “The ability to compute molecular properties using computational techniques, and to dovetail that data with experimental measurements, will generate databases that will produce the most comprehensive results in the molecular sciences.


“There are many laboratories around the world working in this space; however, there are few organizational structures available that encourage open sharing of these data for the benefit of the community and the common good. We seek to collaborate with others to provide this structure; an open knowledge network or repository where scientists can deposit their molecular-level experimental and computational data in exchange for user-friendly tools to help manage and query the data.”


The initial response to their idea has been strong from potential partners. Ferri and the others have already collected more than a dozen letters from major corporations such as Dow and Merck expressing interest in participating. Also on board are Idaho National Laboratory and Argonne National Laboratory, as well as national chemical engineering and chemistry organizations.


McQuade said that chemical engineers in major industries including consumer products and oil and gas producers expend a lot of effort running experiments to determine the molecule they want to use, such as finding the best shampoo additive that doesn’t make babies cry. “The ability to design the properties you want is still more art than science.”


The team also plans to develop a toolkit for processing and visualizing the data.

Roitberg, whose research focuses include advanced visualization, said this could take the form of a virtual reality realm in which a user could find materials that are soluble in water but not oil, for instance, and then be able to browse for similar materials nearby. “We envision a very interactive platform where the user can explore relations between data and desired material properties,” he said. 

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2 min

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3 min

Neutrons by the trillions: Using computational physics to understand nuclear reactors

Zeyun Wu, Ph.D., associate professor in the mechanical and nuclear engineering department at VCU Engineering, is reshaping the future of nuclear power. Nuclear reactors are among the most complex engineered systems on earth, with different physical processes interacting simultaneously across various scales. Even the world's most powerful computers cannot simulate every detail of an operating reactor at once. With a background in computational reactor physics, Wu’s research develops modeling and simulation techniques crucial to understanding next-generation nuclear reactors. By creating these advanced tools, his research eliminates the need for costly physical experimentation while ensuring the safety, efficiency and environmental sustainability of future nuclear power plants. Wu's research focuses on understanding reactor behavior through two aspects: multi-physics and multi-scale modeling. The multi-physics approach integrates various physical phenomena, such as nuclear physics reactions, fluid dynamics, heat transfer and structural mechanics, into a unified simulation framework. The multi-scale modeling technique addresses the vast range of physical scales involved, from subatomic neutron interactions to meter-sized reactor components. Wu’s research can simulate the complex phenomena within reactors at different scales. These models, developed using advanced numerical methods, help predict reactor behavior under various conditions. One of the models Wu uses tracks neutron behavior, a fundamental aspect to understand nuclear reactions. His simulations track trillions of neutrons as they move through various reactor materials, cause fission events and generate power. "What drives power is actually the neutron," explained Wu. "Once an atom splits, along with the nuclear energy release, lots of neutrons come out. We're talking about 1012 to 1013 neutrons per second. 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Undergraduate and master’s students learn to use established nuclear simulation codes to analyze reactor problems – skills highly valued in the industry and national labs. Ph.D. students build on theoretical foundations to deepen their understanding, enhance existing models, and develop new ones. “My area of research has been continually evolving for the past 60 years or so,” said Wu. “Most of the codes we use have been developed by national labs, like Oak Ridge National Lab, but these codes aren’t perfect. National labs hire Ph.D. level students with this niche to identify deficits in the code, correct errors and even add new functions and improve them.” Looking forward, Wu hopes his research will have a real-world impact on the upcoming shift in nuclear power in America. Over the next 20 to 30 years, the nation's approximately 90 light-water-cooled nuclear reactors reach the end of their operational lifetimes. Light water refers to ordinary water (H₂O), used in most existing reactors to both cool the system and slow down neutrons to sustain the nuclear reaction. To replace them, experts are looking toward advanced, non-light-water-cooled reactors, such as the Molten Uranium Breeder Reactor (MUBR) shown in the figure. Computational methods and tools like Wu’s research lab developed will be essential to their development and implementation. Non-light-water cooled reactors offer significant advantages over the older designs. Some can operate at higher temperatures while others produce substantially less nuclear waste, addressing one of the industry's persistent challenges. "Unlike traditional water reactors, where we have decades of operational experience and established analysis tools, these new designs present unique challenges," explained Wu. 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6 min

College of Engineering researchers develop technology to increase production of biologic pharmaceuticals for diabetes treatment

Chemical and Life Science Engineering Professor Michael “Pete” Peters, Ph.D., is investigating more efficient ways to manufacture biologic pharmaceuticals using a radial flow bioreactor he developed. With applications in vaccines and other personalized therapeutic treatments, biologics are versatile. Their genetic base can be manipulated to create a variety of effects from fighting infections by stimulating an immune response to weight loss by producing a specific hormone in the body. Ozempic, Wegovy and Victoza are some of the brand names for Glucagon-Like Peptide-1 (GLP-1) receptor agonists used to treat diabetes. These drugs mimic the GLP-1 peptide, a hormone naturally produced in the body that regulates appetite, hunger and blood sugar. “I have a lot of experience with helical peptides like GLP-1 from my work with COVID therapeutics,” says Peters. “When it was discovered that these biologic pharmaceuticals can help with weight loss, demand spiked. These drug types were designed for people with type-2 diabetes and those diabetic patients couldn’t get their GLP-1 treatments. We wanted to find a way for manufacturers to scale up production to meet demand, especially now that further study of GLP-1 has revealed other applications for the drug, like smoking cessation.” Continuous Manufacturing of Biologic Pharmaceuticals Pharmaceuticals come in two basic forms: small-molecule and biologic. Small-molecule medicines are synthetically produced via chemical reactions while biologics are produced from microorganisms. Both types of medications are traditionally produced in a batch process, where base materials are fed into a staged system that produces “batches” of the small-molecule or biologic medication. This process is similar to a chef baking a single cake. Once these materials are exhausted, the batch is complete and the entire system needs to be reset before the next batch begins. “ The batch process can be cumbersome,” says Peters. “Shutting the whole process down and starting it up costs time and money. And if you want a second batch, you have to go through the entire process again after sterilization. Scaling the manufacturing process up is another problem because doubling the system size doesn’t equate to doubling the product. In engineering, that’s called nonlinear phenomena.” Continuous manufacturing improves efficiency and scalability by creating a system where production is ongoing over time rather than staged. These manufacturing techniques can lead to “end-to-end” continuous manufacturing, which is ideal for producing high-demand biologic pharmaceuticals like Ozempic, Wegovy and Victoza. Virginia Commonwealth University’s Medicines for All Institute is also focused on these production innovations. Peters’ continuous manufacturing system for biologics is called a radial flow bioreactor. A disk containing the microorganisms used for production sits on a fixture with a tube coming up through the center of the disk. As the transport fluid comes up the tube, the laminar flow created by its exiting the tube spreads it evenly and continuously over the disk. The interaction between the transport medium coming up the tube and the microorganisms on the disk creates the biological pharmaceutical, which is then taken away by the flow of the transport medium for continuous collection. Flowing the transport medium liquid over a disc coated with biologic-producing microorganisms allows the radial flow bioreactor to continuously produce biologic pharmaceuticals. “There are many advantages to a radial flow bioreactor,” says Peters. “It takes minutes to switch out the disk with the biologic-producing microorganisms. While continuously producing your biologic pharmaceutical, a manufacturer could have another disk in an incubator. Once the microorganisms in the incubator have grown to completely cover the disk, flow of the transport medium liquid to the radial flow bioreactor is shut off. The disk is replaced and then the transport medium flow resumes. That’s minutes for a production changeover instead of the many hours it takes to reset a system in the batch flow process.” The Building Blocks of Biologic Pharmaceuticals Biologic pharmaceuticals are natural molecules created by genetically manipulating microorganisms, like bacteria or mammalian cells. The technology involves designing and inserting a DNA plasmid that carries genetic instructions to the cells. This genetic code is a nucleotide sequence used by the cell to create proteins capable of performing a diverse range of functions within the body. Like musical notes, each nucleotide represents specific genetic information. The arrangement of these sequences, like notes in a song, changes what the cell is instructed to do. In the same way notes can be arranged to create different musical compositions, nucleotide sequences can completely alter a cell’s behavior. Microorganisms transcribe the inserted DNA into a much smaller, mRNA coded molecule. Then the mRNA molecule has its nucleotide code translated into a chain of amino acids, forming a polypeptide that eventually folds into a protein that can act within the body. “One of the disadvantages of biologic design is the wide range of molecular conformations biological molecules can adopt,” says Peters. “Small-molecule medications, on the other hand, are typically more rigid, but difficult to design via first-principle engineering methods. A lot of my focus has been on helical peptides, like GLP-1, that are a programmable biologic pharmaceutical designed from first principles and have the stability of a small-molecule.” The stability Peters describes comes from the helical peptide’s structure, an alpha helix where the amino acid chain coils into a spiral that twists clockwise. Hydrogen bonds that occur between the peptide’s backbone creates a repeating pattern that pulls the helix tightly together to resist conformational changes. “It’s why we used it in our COVID therapeutic and makes it an excellent candidate for GLP-1 continuous production because of its relative stability,” says Peters. Programming The Cell Chemical and Life Science Engineering Assistant Professor Leah Spangler, Ph.D., is an expert at instructing cells to make specific things. Her material science background employs proteins to build or manipulate products not found in nature, like purifying rare-earth elements for use in electronics. “My lab’s function is to make proteins every day,” says Spangler. “The kind of proteins we make depends entirely on the project they are for. More specifically I use proteins to make things that don’t occur in nature. The reason proteins don’t build things like solar cells or the quantum dots used in LCD TVs is because nature is not going to evolve a solar cell or a display surface. Nature doesn’t know what either of those things are. However, proteins can be instructed to build these items, if we code them to.” Spangler is collaborating with Peters in the development of his radial flow bioreactor, specifically to engineer a microorganismal bacteria cell capable of continuously producing biologic pharmaceuticals. “We build proteins by leveraging bacteria to make them for us,” says Spangler. “It’s a well known technology. For this project, we’re hypothesizing that Escherichia coli (E. coli) can be modified to make GLP-1. Personally, I like working with E. coli because it’s a simple bacteria that has been thoroughly studied, so there’s lots of tools available for working with it compared to other cell types.” Development of the process and technique to use E. coli with the radial flow bioreactor is ongoing. “Working with Dr. Spangler has been a game changer for me,” says Peters. “She came to the College of Engineering with a background in protein engineering and an expertise with bacteria. Most of my work was in mammalian cells, so it’s been a great collaboration. We’ve been able to work together and develop this bioreactor to produce GLP-1.” Other Radial Flow Bioreactor Applications Similar to how the GLP-1 peptide has found applications beyond diabetes treatment, the radial flow bioreactor can also be used in different roles. Peters is currently exploring the reactor’s viability for harnessing solar energy. “One of the things we’ve done with the internal disc is to use it as a solar panel,” says Peters. “The disk can be a black body that absorbs light and gets warm. If you run water through the system, water also absorbs the radiation’s energy. The radial flow pattern automatically optimizes energy driving forces with fluid residence time. That makes for a very effective solar heating system. This heating system is a simple proof of concept. Our next step is to determine a method that harnesses solar radiation to create electricity in a continuous manner.” The radial flow bioreactor can also be implemented for environmental cleanup. With a disk tailored for water filtration, desalination or bioremediation, untreated water can be pushed through the system until it reaches a satisfactory level of purification. “The continuous bioreactor design is based on first principles of engineering that our students are learning through their undergraduate education,” says Peters. “The nonlinear scaling laws and performance predictions are fundamentally based. In this day of continued emphasis on empirical AI algorithms, the diminishing understanding of fundamental physics, chemistry, biology and mathematics that underlie engineering principles is a challenge. It’s important we not let first-principles and fundamental understanding be degraded from our educational mission, and projects like the radial flow bioreactor help students see these important fundamentals in action.”

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