2010 Dennis A. Dougherty, Caltech

Professor Dennis A. Dougherty received his B.S. and M.S. degrees from Bucknell University in 1974. He did his doctoral research at Princeton University with Kurt Mislow and a year of post-doctoral studies with Jerome Berson at Yale University. Dougherty joined the faculty in the Division of Chemistry and Chemical Engineering at the California Institute of Technology in 1979, where he is now the George Grant Hoag Professor of Chemistry.

Dougherty is perhaps best known for development of the cation-? interaction, a novel but potent binding interaction between molecules that plays a central role in establishing protein structures and in modulating drug-receptor interactions. The fundamental nature of the interaction was established through extensive theoretical and model studies by the Dougherty group. Dougherty also established the prevalence of the cation-? interaction in biological systems, and it is now recognized to be important in a wide range biological processes.

More recently, Dougherty has addressed molecular neurobiology, applying the mindset and tools of physical organic chemistry to the complex proteins of neuroscience – the molecules of memory, thought, and sensory perception; of Alzheimer’s, Parkinson’s, and schizophrenia. Target receptors include the nicotinic acetylcholine receptor, the 5-HT3 (serotonin) receptor, and the D2 dopamine receptor. Through these efforts, Dougherty has produced fundamental insights into drug-receptor interactions, including cation- interactions.

Dougherty is a member of the National Academy of Sciences, and a fellow of the American Association for the Advancement of Science and the American Academy of Arts and Science. He has been recognized with a number of awards, including the ACS James Flack Norris Award for Physical Organic Chemistry, the AstraZeneca Excellence in Chemistry Award, the Arthur C. Cope Scholar Award, and has been designated a Javits Neuroscience Investigator by NIH. He is also the co-author, with Professor Eric Anslyn, of the influential textbook, Modern Physical Organic Chemistry.

Abstract: The human brain is the most complex object known to man. It presents daunting challenges at all levels, from the anatomical, to the cellular, to the molecular. Our work seeks to provide a chemical-scale understanding of the molecules of memory, thought, and sensory perception; of Alzheimer’s, Parkinson’s, and schizophrenia. An area of particular interest has been the chemistry of nicotine addiction. The initial chemical event of nicotine addiction involves nicotine binding to and activating acetylcholine (ACh) receptors in the brain. Using the mindset and methodologies of physical organic chemistry, we have probed these complex membrane proteins with a precision and subtlety normally associated with small molecule studies. We have established that the cation- interaction plays a pivotal role in promoting the high potency of nicotine in the brain, leading to its addictive properties. We have also discovered key hydrogen bonding interactions that uniquely contribute to the binding of nicotine to ACh receptors. These chemical studies provide a high-precision structural model for the interaction of potent drugs at brain receptors.

Cost: The entrée is Smoked Paprika and Garlic Roasted Free Range Chicken with sweet potato hash, haricots verts and roast chicken jus. The cost is $53 including salad, dessert, wine with dinner, tax and tip, payable at the door with cash or check.

Reservations: Please call Nancy Paradiso in the Section Office at (310) 327–1216 or email office@scalacs.org by Wednesday, April 20, 2011.

Directions: A campus map and directions to the Athenaeum are available at http://www.its.caltech.edu/~ath/pdf/Athenaeum_map.LH.pdf .