Dennis A. Dougherty
Assistant: Aracely Sustaita
The Dougherty group in the Division of Chemistry and Chemical Engineering at the California Institute of Technology conducts research in organic chemistry and chemical biology. The major focus of the group seeks a chemical-scale understanding of ion channels and neuroreceptors. These integral membrane proteins are the molecules of memory, learning, and sensory perception. They are also the targets of pharmaceuticals intended to treat Alzheimers disease, Parkinsons disease, schizophrenia, learning and attention deficits, and many others disorders. By using a combination of organic synthesis, molecular biology, electrophysiology, and computer modeling, detailed structural and mechanistic insights into these complex systems can be obtained.
Ion channels are also the ultimate molecular sensors. These proteins transduce a chemical event - binding of a small organic molecule - into an electrical signal (flow of ions). The sensitivity of modern electronics allows single molecule detection to be routinely achieved. As such, another goal of the group is to use ion channels as a platform for developing novel signaling/sensing systems.
We also have a long-standing interest in fundamental aspects of biological recognition, and have extensively studied the cation-p interaction as an important general force in structural biology. We continue to evaluate new systems that provide examples of this important and broadly general noncovalent binding interaction.
Publications
- Haloi, Nandan;Huang, Shan et al. (2024) Interactive computational and experimental approaches improve the sensitivity of periplasmic binding protein-based nicotine biosensors for measurements in biofluidsProtein Engineering, Design and Selection
- Walker, Noah B.;Yan, Yijin et al. (2023) β2 nAChR Activation on VTA DA Neurons Is Sufficient for Nicotine Reinforcement in RatseNeuro
- Nichols, Aaron L.;Blumenfeld, Zack et al. (2023) Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and MembraneJournal of Neuroscience
- Haloi, Nandan;Huang, Shan et al. (2023) Interactive computational and experimental approaches improve the sensitivity of periplasmic binding protein-based nicotine biosensors for measurements in biofluids
- Lummis, Sarah C. R.;Dougherty, Dennis A. (2022) Expression of Mutant Glycine Receptors in Xenopus Oocytes Using Canonical and Non-Canonical Amino Acids Reveals Distinct Roles of Conserved Proline ResiduesMembranes
- Knox, Hailey J.;Rego Campello, Hugo et al. (2022) Characterization of Binding Site Interactions and Selectivity Principles in the α3β4 Nicotinic Acetylcholine ReceptorJournal of the American Chemical Society
- Nichols, Aaron L.;Blumenfeld, Zack et al. (2022) Selective Serotonin Reuptake Inhibitors Within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane
- Mocatta, James;Mesoy, Susanne M. et al. (2022) 5-HT₃ Receptor MX Helix Contributes to Receptor FunctionACS Chemical Neuroscience
- Muthusamy, Anand K.;Kim, Charlene H. et al. (2022) Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-Methadone for Use in Cells, Organelles, and BiofluidsJournal of the American Chemical Society
- Nichols, Aaron L.;Blumenfeld, Zack et al. (2022) Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligandseLife