Dennis A. Dougherty

George Grant Hoag Professor of Chemistry
Division of Chemistry and Chemical Engineering

California Institute of Technology, 164-30
Pasadena, California 91125
626 395 6089 FAX: 626 564 9297
dadougherty@caltech.edu

B.S., M.S., 1974, Bucknell University;
Ph.D., 1978, Princeton University; (Kurt Mislow)
Postdoctoral Fellow, 1979, Yale University (Jerome Berson).

Caltech:
Assistant Professor: 1979 - 1985
Associate Professor: 1985 - 1989
Professor: 1989 - 2001
Executive Officer for Chemistry: 1994 - 1999
Hoag Professor: 2002 -

Awards and Honorary Societies
Phi Beta Kappa
Fellow of the Alfred P. Sloan Foundation (1983-1985)
Camille and Henry Dreyfus Teacher-Scholar (1984-1989)
ASCIT Excellence in Teaching Award (1987)
AstraZeneca Excellence in Chemistry Award (1991)
Richard Badger Teaching Award (1992)
Arthur C. Cope Scholar Award (1992)
Fellow of the American Association for the Advancement of Science (1994)
Fellow of the American Academy of Arts and Sciences (1999)
ASCIT Excellence in Teaching Award (2000)
Javits Neuroscience Investigator, NIH (2004)

Selected Lectureships
Gassman Lecturer, University of Minnesota (2002)
Alexander Todd Visiting Professor, Cambridge University (2001)
Büchi Lecturer in Organic Chemistry, MIT (2001)
Kharash Visiting Professorship, University of Chicago (2000)
Blomquist Lectures, Cornell University (2000)
Watkins Lectures, Wichita State University (2000)
Fuson Visiting Scholar, University of Illinois (1999)
Frontiers in Chemical Research, Texas A&M University (1999)

Textbook
Modern Physical Organic Chemistry, E.V. Anslyn and Dennis A. Dougherty, University Science Books, Sausalito, CA, 2006.

Selected Recent Publications

Electrostatic Contributions of Aromatic Residues in the Local Anesthetic Receptor of Voltage-gated Sodium Channels, C. A. Ahern, A. L. Eastwood, D. A. Dougherty, and R. Horn, Circulation Res., 2008, 102, 86-94.

Confirming the Revised C-terminal Domain of the MscL Crystal Structure, J. A. Maurer, D. E. Elmore, D. Clayton, H. A. Lester, D. A. Dougherty, Biophys.J., in press.

Improved Amber and Opal Suppressor tRNAs for Incorporation of Unnatural Amino Acids In Vivo, Part 2: Evaluating Suppression Efficiency, E. A. Rodriguez, H. A. Lester, D. A. Dougherty, RNA, 2007, 13, 1715-1722.

Improved Amber and Opal Suppressor tRNAsfor Incorporation of Unnatural Amino AcidsIn Vivo, Part 1: Minimizing Misacylation, E. A. Rodriguez, H. A. Lester, D. A. Dougherty, RNA, 2007, 13, 1703-1714.

1-Oxo-5-hydroxytryptamine: A Surprisingly Potent Agonist of the 5-HT3 (Serotonin) Receptor. S. M. A. Kedrowski, K. S. Bower, D. A. Dougherty, Org. Lett., 2007, 9, 3205-3207.

5-Fluorotryptamine is a partial agonist at 5-HT3 receptors, and reveals that size and electronegativity at the 5 position of tryptamine are critical for efficient receptor function. K. S. Bower, K. L.Price, L. E. Sturdee, D. A. Dougherty, S. C. R. Lummis, Eur. J. Pharm., 2008, 580, 291-297.

Reconstitution of Ion Channels in Agarose-Supported Silicon Orifices, J. A. Maurer, V. E. White, D. A. Dougherty, J. L. Nadeau, Biosensors Bioelectronics, 2007, 22, 2577-2584.

Calcium Block of Single Sodium Channels. Role of a Pore-lining Aromatic Residue, V. P. Santarelli, A. L. Eastwood, D. A. Dougherty, C. A. Ahern, R. Horn, Biophys. J., 2007, 93, 2341-2349.

Establishing an Ion Pair in the GABA_C Receptor that Contributes to the Gating Pathway, J. Wang, H. A. Lester, D. A. Dougherty, J. Biol. Chem., 2007, 282, 26210-26216.

A Cation-π Interaction Discriminates Among Sodium Channels that are either Sensitive or Resistant to Tetrodotoxin Block, V. P. Santarelli, A. L. Eastwood, D. A. Dougherty, R. Horn, C. A. Ahern, J. Biol. Chem., 2007, 282, 8044-8051.

Chemical-Scale Studies on the Role of a Conserved Aspartate in Preorganizing the Agonist Binding Site of the Nicotinic Acetylcholine Receptor,  A. L. Cashin, M. M. Torrice, K. A. McMenimen, H. A. Lester, D. A. Dougherty, Biochemistry, 2007, 46, 630-639.

Unnatural Amino Acid Mutagenesis of the GABA_A Receptor Binding Site Residues Reveals a Novel Cation-π Interaction Between GABA and b2 Tyr97. Padgett C.L., Hanek A.P., Lester H.A., Dougherty D.A. and Lummis S.C.R., J. Neurosci., 2007, 27, 886-892.

A Cation-π Interaction between Extracellular TEA and an Aromatic Residue in Potassium Channels, C. A. Ahern, A. L. Eastwood, H. A. Lester and D. A. Dougherty  and Richard Horn, J. Gen. Phys. 2006, 128, 649-657.

Probing the Mg²⁺ Blockade Site of an NMDA Receptor with Unnatural Amino Acid Mutagenesis, K. A. McMenimen, E. J. Petersson, H. A. Lester, D, A. Dougherty  ACS Chem.^. Biol., 2006, 1, 227-234.

Voltage-Dependent Hydration and Conduction Properties of the Hydrophobic Pore of the MscS Channel. S. A. Spronk, D. E. Elmore, D. A. Dougherty, Biophys. J., 2006, 90, 3555-3569.

In Vivo Incorporation of Multiple Unnatural Amino Acids Using Nonsense and Frameshift Suppression.  E. A. Rodriguez, H. A. Lester, and D. A. Dougherty, Proc. Natl. Acad. Sci. (USA), 2006, 103, 8650-8655.

A Unified View of the Role of Electrostatic Interactions in Modulating the Gating of Cys Loop Receptors. Xinan Xiu, Ariele P. Hanek, Jinti Wang, Henry A. Lester, and Dennis A. Dougherty, J. Biol. Chem., 2005, 280, 41655-41666.

A Cation-pi Binding Interaction with a Tyrosine in the Binding Site of the GABAC Receptor. Sarah CR Lummis, Darren L Beene, Neil J. Harrison, Henry A. Lester, and Dennis A. Dougherty, Chem. Biol. 2005, 12, 993-997.

Cis-trans Isomerization at a Proline Opens the Pore of a Neurotransmitter-gated Ion Channel. Sarah C.R. Lummis, Darren L. Beene, Lori W. Lee, Henry A. Lester, R. William Broadhurst, and Dennis A. Dougherty, Nature, 2005, 438, 248-252.

Caged Phosphoproteins Deborah M. Rothman, E. James Petersson, M. Eugenio Vázquez, Gabriel S. Brandt, Dennis A. Dougherty*, Barbara Imperiali1* J. Am. Chem. Soc., 2005, 127, 846-847.

Using Physical Chemistry to Differentiate Nicotinic from Cholinergic Agonists at the Nicotinic Acetylcholine Receptor, Amanda L. Cashin, E. James Petersson, Henry A. Lester, and Dennis A. Dougherty J. Am. Chem. Soc., 2005, 127, 350-356.

Cys-loop Receptors: New Twists and Turns H, A. Lester, M. I. Dibas, D. S. Dahan, J. F. Leite and D. A. Dougherty Trends Neurosci, 2004, 27, 329-336.

Tyrosine Residues That Control Binding and Gating in the 5-Hydroxytryptamine3 Receptor Revealed by Unnatural Amino Acid Mutagenesis. Darren L Beene, Kerry L Price, Henry A Lester, Dennis A Dougherty & Sarah CR Lummis, J. Neurosci., 2004, 24, 9097-9104.

A fluorophore attached to nicotinic acetylcholine receptor bM2 detects productive binding of agonist to the ad site. D.S. Dahan, V. A. Auyeung, D. A. Dougherty, and H. A. Lester, Proc. Natl. Acad. Sci. (USA), 2004, 101, 10195-10200.

Total chemical synthesis, vesicle-reconstitution and electrophysiological characterization of the mechanosensitive channels of large conductance from Escherichia coli and Mycobacterium Tuberculosis. D. Clayton, G. Shapovalov, J. A. Maurer, D. A. Dougherty, H. A. Lester and G. Kochendoerfer, Proc. Natl. Acad. Sci. (USA), 2004, 101, 4764-4769.

Investigation of Apparent Mass Deviations in Electrospray Ionization Tandem Mass Spectrometry of a Benzophenone Labeled Peptide John F. Leite, Dennis A. Dougherty, Henry A. Lester and Mona Shahgholi, Rapid Comm. Mass Spect., 2003, 17, 1677-1684

Identification of Nicotinic Acetylcholine Receptor a1 Gating-Dependent Molecular Motions Using Electrophysiology-Coordinated Photochemistry and Mass Spectrometry. J. F. Leite, M. P. Blanton, M. Shahgholi, D. A. Dougherty, and H. A. Lester, Proc. Natl. Acad. Sci. USA, 2003, 100, 13054-13059.

Investigating Lipid Composition Effects on the Mechanosensitive Channel of Large Conductance (MscL) Using Molecular Dynamics Simulations Donald E. Elmore and Dennis A. Dougherty, Biophysical J., 2003, 85, 1512-1524

Unnatural Amino Acid Mutagenesis in Mapping Ion Channel Function. D. L. Beene, D. A. Dougherty, and H. A. Lester, Curr. Opin. Neurobiol. 2003, 13, 264-270.

Site-specific Incorporation of Unnatural Amino Acids into Receptors Expressed in Mammalian Cells. S. L. Monahan, H. A. Lester, and D. A. Dougherty, Chem. Biol., 2003, 10, 573-580.

Different Binding Orientations for the Same Agonist at Homologous Receptors: A Lock and Key or a Simple Wedge? T. W. Mu, H. A. Lester, and D. A. Dougherty, J. Am. Chem. Soc., 2003, 125, 6850-6851.

Generation and Evaluation of a Large Mutational Library from the Escherichia coli Mechanosensitive Channel of Large Conductance, MscL: Implications for Channel Gating and Evolutionary Design. J. A. Maurer and D. A. Dougherty, J. Biol. Chem., 2003, 278, 21076-21082.

Caging Proteins Through Unnatural Amino Acid Mutagenesis. E. J. Petersson, G. S. Brandt, N. M. Zacharias, D. A. Dougherty, and H. A. Lester, Methods in Enzymololgy, 2003, 360, 258-73.

A Perturbed pKa at the Binding Site of the Nicotinic Acetylcholine Receptor: Implications for Nicotine Binding. E. J. Petersson, A. Choi, D. S. Dahan, H. A. Lester, and D. A. Dougherty, J. Am. Chem. Soc., 2002, 124, 12662-12663.

Cation-pi Interactions in Ligand Recognition at Serotonergic (5-HT3A) and Nicotine Acetylcholine Receptors. The Anomalous Binding Properties of Nicotine. D. L. Beene, G. S. Brandt, W. Zhong, N. M. Zacharias, H. A. Lester, and D. A. Dougherty, Biochemistry, 2002, 41, 10262-10269.

Cation-pi Interactions in Ligand Recognition and Catalysis. N. Zacharias and D. A. Dougherty, Trends Pharmacol. Sci., 2002, 23 (6), 281-287.

MALDI-TOF Mass Spectrometry Methods for Evaluation of in vitro Aminoacyl tRNA Production. E. J. Petersson, M. Shahgholi, H. A. Lester, and D. A. Dougherty, RNA, 2002, 8, 542-547.

A High-Throughput Screen for MscL Channel Activity and Mutational Phenotyping. J. A. Maurer and D. A. Dougherty, Biochim. Biophys. Acta, 2001, 1514, 165-169.

Incorporation of Caged Cysteine and Caged Tyrosine into a Transmembrane Segment of the Nicotinic Acetylcholine Receptor. K. D. Philipson, J. P. Gallivan, G. S. Brandt, D. A. Dougherty, and H. A. Lester. Am. J. Physiol Cell Physiol, 2001, 281, C195-C206.

Molecular Dynamics Simulations of Wild type and Mutant Forms of the M. tuberculosis MscL Channel. D. E. Elmore and D. A. Dougherty, Biophys. J., 2001, 81, 1345-1359.

Tyrosine Decaging Leads to Substantial Membrane Trafficking during Modulation of an Inward Rectifier Potassium Channel. Y. Tong, G. S. Brandt, M. Li, G. Shapovalov, E. Slimko, A. Karschin, D. A. Dougherty, and H. A. Lester, J. Gen. Phys., 2001, 117, 103-118.

The Tethered Agonist Approach to Mapping Ion Channel Proteins — Toward a Structural Model for the Agonist Binding Site of Nicotinic Acetylcholine Receptor. L. Li, W. Zhong, N. Zacharias, C. Gibbs, H. A. Lester, and D. A. Dougherty, Chem. Biol., 2001, 8, 47-58.

Comparing and Contrasting Escherichia coli and Mycobacterium tuberculosis Mechanosensitive Channels (MscL). New Gain of Function Mutations in the Loop Region. J. A. Maurer, D. E. Elmore, H. A. Lester, and D. A. Dougherty, J. Biol. Chem., 2000, 275 (29), 22238-22244.

A Computational Study of Nicotine Conformations in the Gas Phase and in Water. D. E. Elmore and D. A. Dougherty, J. Org. Chem., 2000, 65 (3), 742-747.

Probing the Role of a Conserved M1 Proline Residue in 5-Hydroxytryptamine3 Receptor Gating. H. Dong, P. M. England, S. S. Farivar, D. A. Dougherty, and H. A. Lester, Mol. Pharmacol., 2000, 57, 1114-1122.

Mapping Disulfide Connectivity Using Backbone Ester Hydrolysis. P. M. England, H. A. Lester, and D. A. Dougherty, Biochemistry, 1999, 38, 14409-14415.

A Computational Study of Cation-pi Int Interactions vs. Salt Bridges in Aqueous Media: Implications for Protein Engineering. J. P. Gallivan and D. A. Dougherty, J. Am. Chem. Soc., 2000, 122 (5), 870-874.

Cation-pi Interactions in Structural Biology. J. P. Gallivan and D. A. Dougherty, Proc. Natl. Acad. Sci. USA, 1999, 96, 9459-9464.

Incorporation of Esters into Proteins: Improved Synthesis of Hydroxyacyl tRNAs. P. M. England, H. A. Lester, D. A. Dougherty, Tetrahedron Lett.,1999, 40, 6189-6192.

Backbone Mutations in Transmembrane Domains of a Ligand-Gated Ion Channel: Implications for the Mechanism of Gating. P. M. England, Y. Zhang, D. A. Dougherty, and H. A. Lester, Cell, 1999, 96, 89-98.

A Selective Receptor for Arginine Derivatives in Aqueous Media. Energetic Consequences of Salt Bridges that are Highly Exposed to Water. S. M. Ngola, P. C. Kearney, S. Mecozzi, K. Russell, and D. A. Dougherty, J. Am. Chem. Soc., 1999, 121, 1192-1201.

From Ab Initio Quantum Mechanics to Molecular Neurobiology: A Cation-pi Binding Site in the Nicotinic Receptor. W. Zhong, J. P. Gallivan, Y. Zhang, L. Li, H. A. Lester, and D. A. Dougherty, Proc. Natl. Acad. Sci. (USA), 1998, 95, 12088-12093.

Flash Decaging of Tyrosine Sidechains in an Ion Channel. J. C. Miller, S. K. Silverman, P. M. England, D. A. Dougherty, and H. A. Lester, Neuron, 1998, 20, 619-624.

In Vivo Incorporation of Unnatural Amino Acids into Ion Channels in a Xenopus Oocyte Expression System. M. W. Nowak, J. P. Gallivan, S. K. Silverman, C. G. Labarca, D. A. Dougherty, and H. A. Lester, in Methods in Enzymology, 1998, 293, Ion Channels, Part B, E. P. Conn, Ed., Academic Press: San Diego, pp. 504-529.

Site-Specific Incorporation of Biotinylated Amino Acids as a Means to Identify Surface Exposed Residues in Integral Membrane Proteins. J. P. Gallivan, H. A. Lester, and D. A. Dougherty, Chem. Biol., 1997, 4, 739-749.

Is the Brain Ready for Physical Organic Chemistry? D. A. Dougherty, J. Phys. Org. Chem., 1998, 11, 334-340.

Site-Specific, Photochemical Proteolysis Applied to Ion Channels In Vivo. P. M. England, H. A. Lester, N. Davidson, and D. A. Dougherty, Proc. Natl. Acad. Sci. (USA), 1997, 94, 11025-11030.

The Cation-pi Interaction. J. C. Ma and D. A. Dougherty, Chem. Rev., 1997, 97, 1303-1324.

Determinants of Nicotinic Receptor Gating in Natural and Unnatural Side Chain Structures at the M2 9’ Position. P. C. Kearney, H. Zhang, W. Zhong, D. A. Dougherty, and H. A. Lester, Neuron, 1996,17, 1221-1229.

Cation-pi Interactions in Aromatics of Biological and Medicinal Interest: Electrostatic Potential Surfaces as a Useful Qualitative Guide. S. Mecozzi, A. P. West, Jr., and D. A. Dougherty, Proc. Natl. Acad. Sci. USA, 1996, 93, 10566-10571.

Evidence for the Importance of Polarizability in Biomimetic Catalysis Involving Cyclophane Receptors. S. M. Ngola and D. A. Dougherty, J. Org. Chem., 1996, 61, 4355-4360.

Cation-pi Interactions in Simple Aromatics. Electrostatics Provide a Predictive Tool. S. Mecozzi, A. P. West, Jr., and D. A. Dougherty, J. Am. Chem. Soc., 1996, 118, 2307-2308.

Cation-pi Interactions in Chemistry and Biology. A New View of Benzene, Phe, Tyr, and Trp. D. A. Dougherty, Science, 1996, 271, 163-168.

Nicotinic Receptor Binding Site Probed with Unnatural Amino-Acid Incorporation in Intact Cells. M. W. Nowak, P. C. Kearney, J. R. Sampson, M. E. Saks, C. G. Labarca, S. K. Silverman, W. Zhong, J. Thorson, J. N. Abelson, N. Davidson, P. G. Schultz, D. A. Dougherty, and H. A. Lester, Science, 1995, 268, 439-442.