Cyber Chemistry Project to Speed Drug-Making

National Science Foundation-funded project is aimed at solving dilemma of efficient drug-making from massive data available on the human genome

By Steve Berberich
February 9, 2009

Drug-makers could one day make products faster because of a $2.5 million National Science Foundation (NSF)-funded project now underway at the University of Maryland School of Pharmacy and three other sites.

The cyber-infrastructure project goes to the heart of a current dilemma facing scientists trying to conduct efficient drug discovery and development from the massive data available on the human genome, says Alexander MacKerell, PhD, the Grollman-Glick Professor of Pharmaceutical Sciences at the University of Maryland School of Pharmacy.

Scientists who look for new therapeutic drug opportunities from human gene and protein data have, in turn, created a “huge number of computational tools based on the mathematical models and parameters to biological molecules,” says MacKerell, who is director of the Computer-Aided Drug Design Center at the School of Pharmacy and principal investigator for the project. But, he says, such software tools are not one-size-fits-all. They are designed for different categories of molecules.

“Right now it is very tedious and time consuming to set up these mathematical models and parameters for the new molecules. Our cyber infrastructure will make this much faster. We are going to put the parameter engine in place to do the work for the scientist.”

Also funded for the cyber-infrastructure project are the Universities of Kentucky, Florida, and Illinois. Across the four universities, the project will also have applications in facilitating the design of electronics and the study of a wide range of material science and biological systems at the most basic level, in addition to drug design applications.

The project is aimed toward putting the parameter engine online. Researchers will go to the Internet, enter their drug molecule, and get the best model and the correct parameters for making their investigation more efficient. The proposed engine will provide an open architecture for obtaining and testing parameters under various conditions.

Ordinarily, once a drug company identifies a new drug candidate for the treatment of a particular medical problem, the next step is optimizing the drug candidate to improve its therapeutic potential. This is a huge task that involves testing hundreds of molecules, a task that can be facilitated using computational tools, says MacKerell. “We are trying to allow for computational tools to be rapidly applied to large numbers of molecules. We want to automate this process. To do so will allow computational scientists to work with biologists, thereby decreasing the time and cost required to develop new drug candidates.”

Also, the project will include annual workshops for education and outreach.

The basis for the Computer-Aided Drug Design Center is to ease the discovery of novel therapeutic agents that combines rational drug design methods with chemistry and structural biology. The computer-aided drug design approach allows researchers to use information available in 3-D structures of biological target molecules, which may be associated with human diseases, to identify chemicals that have a great potential for binding to those target molecules. Chemical compounds developed by such steps can often be developed into research tools and/or therapeutic agents. The NSF cyber-infrastructure project will help make this potential a reality.

Robert Latour, PhD, the McQueen-Quattlebaum Professor of Bioengineering at Clemson University, wrote a letter to the NSF supporting the project “because this is very important for a much broader spectrum of applications. It has enormous potential down the road to design things at the atomic level,” he said. Latour uses the same computational chemistry technology to simulate the interactions between biological molecules, such as proteins, and synthetic materials at the atomic level, aimed toward developing more accurate devices to detect biowarfare agents, more biocompatible implants for the human body, and other bionanotechnology applications.