September 4, 2018 | ASRC News, Structural Biology Initiative

Many proteins, the workhorses of the cell, can be artificially controlled for biotech and therapeutic applications using small chemical compounds. With a three-year, $633,000 grant from the National Science Foundation, researchers at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York are exploring ways to speed up the process to identify which proteins are particularly amenable to such control and determine the mechanisms of such regulation.

To do so, the research team led by Kevin H. Gardner, founding director of the ASRC’s Structural Biology Initiative and Einstein Professor of Chemistry and Biochemistry at The City College of New York, is investigating novel experimental approaches to detect small molecule binding sites – the areas where proteins latch on to certain molecules that are essential to their function. The researchers use pressurized water to probe the protein for binding sites.

“We essentially ‘squeeze’ the protein to get water into areas that it wouldn’t normally go,” Gardner says. “We can then use nuclear magnetic resonance [NMR] to image inside the protein and identify potential binding sites.” The new technique could reduce the time needed to probe a protein from years to days, Gardner says. With this new technique, Gardner and his research team are focusing on proteins associated with cellular sensing of external environmental changes, laying the foundation for partnerships with several other ASRC initiatives.

This technology has the potential to be coupled with novel X-ray crystallography techniques developed by Professor Daniel Keedy (ASRC and CCNY, Biochemistry and Chemistry). His work focuses on a technique to precision-target the binding site once the initial probe has been completed. By marrying both techniques, Gardner hopes to gain a new understanding of how the functions of proteins are controlled, which could be useful for future development of new drug therapies.

Joining Gardner on the research team are doctoral and postdoctoral students, as well as undergraduates from across CUNY who gain hands-on experience with advanced equipment and techniques.