New strategy of defeating cancer

Finding new drugs that can more effectively kill cancer cells or disrupt the growth of tumors is one way to improve survival rates for ailing patients. Increasingly, researchers looking to uncover and test new drugs use powerful supercomputers like those developed and deployed by the Texas Advanced Computing Center (TACC).

"Advanced computing is a cornerstone of drug design and the theoretical testing of drugs," said Matt Vaughn, TACC's Director of Life Science Computing. "The sheer number of potential combinations that can be screened in parallel before you ever go in the laboratory makes resources like those at TACC invaluable for cancer research." Three projects powered by TACC supercomputer, which use virtual screening, molecular modeling and evolutionary analyses, respectively, to explore chemotherapeutic compounds, exemplify the type of cancer research advanced computing enables.

Virtual Screening

Shuxing Zhang, a researcher in the Department of Experimental Therapeutics at the University of Texas MD Anderson Cancer Center, leads a lab dedicated to computer-assisted rational drug design and discovery of novel targeted therapeutic agents. The group develops new computational methods, using artificial intelligence and high-performance computing-based virtual screening strategies, that help the entire field of cancer drug discovery and development.

Identifying a new drug by intuition or trial and error is expensive and time consuming. Virtual screening, on the other hand, uses computer simulations to explore how a large number of small molecule compounds "dock," or bind, to a target to determine if they may be candidates for future drugs.

"In silico virtual screening is an invaluable tool in the early stages of drug discovery," said Joe Allen, a research associate at TACC. "It paints a clear picture not only of what types of molecules may bind to a receptor, but also what types of molecules would not bind, saving a lot of time in the lab."

One specific biological target that Zhang's group investigates is called TNIK (TRAF2- and NCK-interacting kinase). TNIK is an enzyme that plays a key role in cell signaling related to colon cancer. Silencing TNIK, it is believed, may suppress the proliferation of colorectal cancer cells.

Writing in Scientific Reports in September 2016, Zhang and his collaborators reported the results of a study that investigated known compounds with desirable properties that might act as TNIK inhibitors.

"There are a nearly infinite number of possible drug compounds," Vaughn said. "But knowing the principles of what a good drug might look like -- how it might bind to a certain pocket or what it might need to resemble -- helps narrow the scope immensely, accelerating discoveries, while reducing costs."

Zhi Tan, Lu Chen, Shuxing Zhang. Comprehensive Modeling and Discovery of Mebendazole as a Novel TRAF2- and NCK-interacting Kinase Inhibitor. Scientific Reports, 2016; 6 (1) DOI: 10.1038/srep33534