T32 Seminar

Dennis A. Dougherty, PhD

George Grant Hoag Professor of Chemistry
Director, Beckman Institute at Caltech
California Institute of Technology

Monday, April 1st | 4:00 pm
Pancoe Auditorium
Coffee and dessert will be served at 3:45 pm

Abstract:

Chemical Biology on the Brain: Understanding the Nicotine Receptor

While structural studies continue to advance, obtaining detailed insights into small molecule binding interactions to complex, integral membrane receptors of the mammalian central nervous system remain a significant challenge. Using unnatural amino acid mutagenesis and heterologous expression in Xenopus oocytes, we have developed ways to address specific questions concerning drug-receptor interactions and other features of the nicotinic acetylcholine receptors (nAChR), a prototype receptor system. We can semi-quantitatively evaluate cation-π interactions, hydrophobic interactions, and hydrogen bonding interactions, both to amino acid side chains and to the protein backbone. This provides a general strategy for understanding drug-receptor interactions with chemical precision.

Biography:

Dennis A. Dougherty is the George Grant Hoag Professor of Chemistry at the California Institute of Technology and Director of the Beckman Institute at Caltech. After a B.S. at Bucknell University, he earned his Ph.D. at Princeton with Kurt Mislow, and then did postdoctoral work with Jerome Berson at Yale. Dougherty is perhaps best known for the development of the cation-π interaction, a powerful noncovalent binding interaction that is widely employed in both small molecule and macromolecular recognition in biology and chemistry. His current research is focused on molecular neurobiology, applying the mindset and tools of physical organic chemistry to the complex proteins of neuroscience. Target receptors include the nicotinic acetylcholine receptor, the 5-HT3 (serotonin) receptor, and voltage-gated ion channels. A highlight of this work has been the evaluation of the binding modes of nicotine at receptors in the CNS vs. the periphery, revealing the critical role that cation-π interactions play in establishing the addictive properties of nicotine. Dougherty is a member of the National Academy of Sciences, and recognition includes the ACS James Flack Norris Award for Physical Organic Chemistry, the Biopolymers Murray Goodman Award, the Hoffmann Medal of the University of Zurich, and designation as a Javits Neuroscience Investigator by NIH. Dougherty has been recognized with several teaching awards at Caltech, including the Richard Feynman Prize. He is the author, with Eric Anslyn, of the influential textbook Modern Physical Organic Chemistry.

Hosted by CLP Trainee Elizabeth Johnson. This is a required activity for CLP Trainees. Supported by the Chemistry of Life Processes Predoctoral Training Program NIH/ NIGMS 5T32GM105538-06