Dr. Ghislain Deslongchamps leads a small group of researchers at the University of New Brunswick, adapting computational chemistry tools normally used in drug design for discovering new catalysts with a wide range of applications – and not just any kind of catalyst. A catalyst is a small molecule that accelerates a particular chemical reaction. One type of extremely valuable catalyst is one that promotes a chemical reaction to generate a molecule as a single stereoisomer. Stereoisomers are molecules that are identical except that they mirror each other’s structure. The analogy used by Deslongchamps is a pair of gloves. The two gloves are exactly the same except that the left glove is a mirror image of the right; each glove can only fit its respective hand. The same applies to drug molecules and how they interact with the body, so they typically need to be produced in the correct “handedness” in order to be safe and effective. For example, thalidomide was a drug sold in the late 1950’s to treat morning sickness in pregnant women. It was manufactured as a 50:50 mixture of its two stereoisomers; one had the desired medicinal properties whereas the other was later found to cause severe birth defects. Thus, the ability to manufacture drugs as single stereoisomers has become a critically important issue for the modern pharmaceutical industry. It’s more difficult to make a molecule as a single stereoisomer, however, Deslongchamps is developing computer-based tools and methods for doing just that – developing asymmetric organocatalysts (purely metal-free organic catalysts) that can produce a molecule of “single handedness”. His is the only research group in the world retraining computer-based drug design tools for the purpose of organocatalyst discovery. Because organocatalysts are metal-free, they may produce less toxic and more environmentally sound drugs, important components of green chemistry. While the catalysts he is designing are of great interest to the pharmaceutical industry, Deslongchamps’s computational tools can also be applied to many other areas where molecules with very specific chemical shapes, features and properties are required. The tools he’s creating — one called “reverse-docking” and the other called “virtual screening” – are inspired by those used in computer-assisted drug design. The computations carried out in his lab can be extremely time onerous and require very advanced computing resources. “We are extremely fortunate to be part of ACENET and having access to the Compute Canada resources to do the research that we do,” Deslongchamps says. “A lot of the work we do might otherwise take months of calculating as opposed to days. It’s almost impractical to do this research on a single computer.” Deslongchamps has a long-standing collaborative relationship with Chemical Computing Group Inc. (CCG), a leading drug software company based in Montreal. CCG is one of only a handful of such companies in the world and Dr. Deslongchamps is utilizing and adapting their software for designing and discovering new catalysts.
Showcase Tag: Green Chemistry
Unlocking the Secrets of a Vital Plant Hormone
A major high performance computing event may seem like an unusual place to showcase landmark research about plants. But that’s exactly what happened at this year’s High Performance Computing Symposium in Halifax. The research, carried out by a team at Saint Mary’s University in Halifax and the University of Jyväskylä in Finland, has unlocked the secrets of ethylene formation using a rather unconventional tool. The team used the ACENET Data Cave located at SMU to create a virtual 3-D model of the molecules involved in the process; a model that allowed them to visualize the process more accurately. Ethylene is a key hormone in plants – a chemical compound that plays a critical role in causing fruit to ripen. But until recently, the chemical process that created ethylene in plants remained a mystery. For one thing, the biosynthesis process that creates ethylene gives off carbon dioxide along with cyanide, a deadly poison that should kill the enzyme that serves as a catalyst in the ethylene creation process. Dr. Jason Clyburne, a chemistry professor and Canada Research Chair in Environmental Science and Materials at Saint Mary’s University, headed up the research study. It was the first time he has used the ACENET Data Cave as part of his research. “Understanding the reaction mechanisms catalyzed by enzymes is a very difficult process, usually requiring a host of chemical, spectroscopic and other techniques,” says Clyburne. “By creating a visual model in the Data Cave, we were able to examine the active site and its environment. It was an extremely useful tool for us.” A number of developments have come from Clyburne’s landmark research. For one thing, the study confirmed the existence of a molecule called cyanoformate, a fragile and elusive ion long speculated to exist, that neutralizes the deadly properties of cyanide. Cyanoformate is formed when molecules of carbon dioxide and cyanide combine. It breaks down quickly, but before it does it carries the cyanide away from the enzyme before it can cause damage to the plant cell. “We learned how nature handles cyanide, a process that we didn’t really understand before,” says Clyburne. The research has some potential practical applications as well, including a better understanding of how fruit ripens – knowledge that could have major benefits to the global agricultural industry. The cyanoformate process also opens up possibilities for a new carbon capture process that could be used to help combat greenhouse gas emissions. Because cyanoformate forms an extremely weak bond between the carbon dioxide and cyanide, the process is attractive to carbon capture technologies that need to be able to easily transport and then release the carbon dioxide so that it can be recycled cheaply and easily. Because crystal structures are freely available on the Internet in a variety of file formats and can be projected in 3-D using the tools available in the ACEnet Data Cave, Clyburne predicts that this form of research will probably become more commonplace in years to come. “The Data Cave really opened my eyes up to the possibilities of seeing inside a material to explore its properties.