We’ve used Folding@home to produce a lot of results towards drug design, and we’ve listed many of the publications on our Papers page. Several scientists in my lab are interested in drug resistance. As an example, they’re trying to understand how bacteria can develop an immunity to vancomycin, an important antibiotic that’s often used as a last resort. Beta-lactamase is also an important drug target due its ability to break down antibiotics like penicillin, and we hope to be able to design drugs to disable its functionality.
We’ve received several grants to study the ribosome, a large and highly complex molecular machine that manufactures proteins. About half of all antibiotics work by preventing bacterial ribosomes from synthesized important proteins. One of the scientific questions revolving around ribosome is why is there a large tunnel inside it through which proteins exit after being synthesized. We would like to understand the inside surface of this tunnel, as it would be useful to understand how key antibiotics interact with the ribosome. Many scientists are still very uncertain about the function of many proteins attached to the ribosome, so we’ve been studying those as well. The ribosome is so large and complex that it’s really been pushing the boundaries of what we can do on Folding@home.
We have some work published in the drug design arena (for example, see the FKBP work done by Shirts and Jayachandran), but much of what we’re most excited about has not been published yet. We are mainly interest in three areas of computational drug design: cytokine-cytokine receptor interaction inhibition, development of novel chaperone inhibitors, and novel antibiotics to target the ribosome.