A picture is worth 1,000 words when it comes to understanding how things work, but 3D moving pictures are even better. That's especially true for scientists trying to stop cancer by better understanding the proteins that make some chemotherapies unsuccessful.
Researchers for decades have had to rely at best on static images of the key proteins related to recurring cancers.
Now SMU biochemist John G. Wise at Southern Methodist University, Dallas, has brought to life in a moving 3D computer model the structure of human P-glycoprotein, which is thought to contribute to the failure of chemotherapy in many recurring cancers.
"This is a very different approach than has been used historically in the field of protein structure biochemistry," Wise said. "Historically, proteins are very often viewed as static images, even though we know that in reality these proteins move and are dynamic."
The model is a powerful new discovery tool, says Wise, particularly when combined with high-performance supercomputing. The dynamic 3D model already has made it possible for Wise to virtually screen more than 8 million potential drug compounds in the quest to find one that will help stop chemotherapy failure.
So far, the supercomputer search has turned up a few hundred drugs that show promise, and Wise and SMU biochemist Pia Vogel have begun testing some of those compounds in their wet lab at SMU.
"This has been a good proof-of-principle," said Wise, a research associate professor in the SMU Department of Biological Sciences. "We've seen that running the compounds through the computational model is an effective way to rapidly and economically screen massive numbers of compounds to find a small number that can then be tested in the wet lab."