Douglas J. Tobias

Picture of Douglas J. Tobias
Professor, Chemistry
School of Physical Sciences
Ph.D., Carnegie Mellon University, 1991, Chemistry & Biophysics
M.S., University of California, Riverside, 1985, Chemistry
B.S., University of California, Riverside, 1984, Chemistry
Phone: (949) 824-4295
Fax: (949) 824-9920
University of California, Irvine
4118 Natural Sciences 1
Mail Code: 2025
Irvine, CA 92697
Research Interests
Theoretical and Computational Chemistry, Biophysical Chemistry, Atmospheric Chemistry
Academic Distinctions
National Institutes of Health Predoctoral Trainee, 1987-1990
National Institutes of Health National Research Service Award,1991-1993
Elected Fellow of the American Association for the Advancement of Science, 2006
Award for Outstanding Contributions to Undergraduate Education in the School of Physical Sciences, 2009
Postdoctoral Researcher, Department of Chemistry, University of Pennsylvania, 1991-1995
Guest Researcher, NIST Center for Neutron Research, National Institute of Standards and Technology, 1995-1997
Appointed to the UC Irvine Faculty, 1997
Assistant Professor, UC Irvine, 1997-2003
Assosiate Professor, UC Irvine, 2003-2005
Professor, UC Irvine, 2005-present
Visiting Professor, Universite Joseph Fourier, Institut de Biologie Structurale, Grenoble, France, 2007
Research Abstract
Our research involves using atomic-scale computer simulation techniques based on classical and quantum mechanics to study the structure and dynamics of biological molecules and biomimetic materials, and aqueous interfaces with air that are important in atmospheric chemical processes. A substantial portion of our work is devoted to the development, implementation, and optimization of novel simulation methodology and analysis tools.

Current areas of research in our lab include:

Atomistic modeling of interfaces relevant to atmospheric chemistry

The surfaces of aerosol particles are the site of unique chemistry that does not occur in the gas phase or bulk solution environments. For the purpose of quantitative modeling of chemical dynamics in the atmosphere and the contributions of aerosols to the Earth’s radiative balance, and hence, climate, it is essential to know the mechanisms and kinetics of reactions occurring at aerosol-air interfaces. Progress along these lines is limited by the difficulty of probing interfaces experimentally with molecular resolution. We are using force field-based and ab initio MD simulations to provide an atomistic view of molecular structure, electronic structure, and dynamics on the surfaces of model systems meant to mimic atmospheric aqueous and organic aerosol particles. In addition to providing new fundamental insight into the composition and physicochemical properties of aerosol surfaces and their interactions with water and atmospheric trace gases, our simulations are proving useful in the development of novel mechanisms for reactions that could be important in the chemistry of the atmosphere, including acid-base, redox, and photochemical reactions. Our work in this area is carried out under the auspices of AirUCI, an NSF-funded Organized Research Unit, headed by UCI Professor Barbara Finlayson-Pitts, which includes several other UCI faculty, partners at three national labs (Pacific Northwest, Lawrence Berkeley, and Lawrence Livermore), and international associates from New Zealand and the Czech Republic.

Structure and dynamics of proteins in membranes

Membrane proteins comprise roughly a quarter of the genome and the majority of pharmaceutical targets, but relatively few structures of membrane proteins are known, and structure prediction using methods developed for soluble proteins is not yet effective. In order to predict their structures with acceptable accuracy, it is necessary to know how membrane proteins interact with and are assembled in fluid lipid membranes sandwiched between aqueous compartments. We have been developing methods for using MD simulations to refine low-resolution structures of lipid bilayers and membrane proteins using x-ray and neutron diffraction data. In addition, we have been running simulations of large systems (several hundred thousand atoms) containing membrane proteins of known structure in explicit lipid bilayers in order to develop a microscopic description of how the membrane distorts and conforms to embedded proteins, to catalog important protein-lipid interactions, and to identify key protein-lipid-water interactions that are relevant to membrane protein function. Our membrane protein research is carried out in close collaboration with experimentalists in the TEMPO (Theory and Experiments in Membrane Protein Organization) group at UCI, as well as other collaborators elsewhere in the U. S. and in Europe.

Mechanism of voltage-sensing in voltage-gated ion channels

Electrical signals in excitable cells (e.g., neurons) are generated by the flow of ions through protein channels in membranes. In the case of voltage-gated ion channels, ion permeation is controlled by the opening and closing of the ion conducting pores in response to changes in the transmembrane electrical potential. Kv channels are built as tetramers, with each monomer contributing a pore domain and a voltage sensing domain (VSD). The VSD contains the S4 helix, which is rich in positively charged residues, predominantly arginines, for high sensitivity to small changes in transmembrane potential. In spite of the availability of crystal structures and a wide variety of spectroscopic and functional data, the molecular mechanism of voltage gating is still not well understood. The details that remain to be worked out, which we are addressing using MD simulations, include the lipid exposure of the charged residues in the S4 helix, the establishment of the location of the VSD in the closed state of the channel, where and how much the VSD moves through the membrane during membrane depolarization, and the nature of the electromechanical coupling through which the motion of the VSD opens and closes the pore. We are also generating atomistic models for proton channels (Hv1) based on their homology with the VSDs of potassium channels, and using force field-based and quantum mechanical/molecular mechanical (QM/MM) MD simulations to elucidate the mechanism of proton conduction.

Coupling of the dynamics of proteins and their surroundings

Protein function requires motion over a wide range of time and length scales. Both temperature and the solvent environment affect the spectrum of dynamical fluctuations in a protein. We have been using MD simulations to study the influence of the environment (aqueous solutions, glass forming co-solvents, and membranes) on protein dynamics. One of the primary objectives of this work has been to elucidate the effects of the environment on the protein dynamical transition from an inactive, glass-like state at low temperature to the functional, liquid-like state at high temperature. This transition, which is ubiquitous in biopolymers, has been of great interest for more than two decades in large part because of its connection to protein function, which for many proteins ceases when they go into the glass-like state. It has been recognized for some time that the solvent environment plays a key role in determining the transition temperature, and the amplitudes of motion in the liquid-like state, but the details of the protein-solvent coupling are still being worked out. In addition to its intrinsic value, this information is key to understanding how certain organisms protect themselves against low temperature and dehydration, and has applications to biopreservation in the food and pharmaceutical industries. The lipid composition-dependence of membrane protein dynamics is relevant to a wide variety of biological processes that rely on transmembrane signalling.
E. V. Schow, J. A. Freites, P. Cheng, A. Bernsel, G. von Heijne, S. H. White, and D. J. Tobias, Arginine insertion in membranes: on the connection between molecular dynamics simulations and translocon-mediated insertion experiments, J. Membrane Biol., 239, 35-48 (2011).
M. Mihaelescu, R. G. Vaswani, E. Jardon-Valadez, F. Castro-Roman, J. A. Freites, D. L. Worcester, A. R. Chamberlin, D. J. Tobias, and S. H. White, Acyl-chain methyl distributions of liquid-ordered and -disordered membranes, Biophys. J., 100, 1455-1462 (2011).
W. D. Brubaker, J. A. Freites, K. J. Golchert, R. A. Shapiro, V. Morikis, D. J. Tobias, and R. W. Martin, Separating instability from aggregation propensity in gammeS-crystallin variants, Biophys. J., 100, 498-506 (2011).
"Dynamics of SecY Translocons with Translocation-defective Mutations," A.-N. Bondar, C. Munoz de Val, J. A. Freites, D. J. Tobias, and S. H. White, Structure 18, 847-857 (2010). (Featured Article)
"Down-state Model of the Voltage-sensing Domain of a Potassium Channel," E. V. Schow, J. A. Freites, K. Gogna, S. H. White, and D. J. Tobias, Biophys. J. 98, 2857-2866 (2010).
"The Low Temperature Inflection Observed in Neutron Scattering Measurements of Proteins is Due to Methyl Rotation: Direct Evidence Using Isotope Labeling," K. Wood, D. J. Tobias, B. Kessler, D. Oesterhelt, G. Zaccai, F. A. A. Mulder, and M. Weik, J. Am. Chem. Soc. 132,4990-4991 (2010).
"Surface Organization of Aqueous MgCl2 and Application to Atmospheric Marine Aerosol Chemistry," N. N. Casillas-Ituarte, K. M. Callahan, C. Y. Tang, X. Chen, M. Roeselova, D. J. Tobias, and H. C. Allen, Proc. Natl. Acad. Sci. USA 107, 6616-6621 (2010).
"Structure and hydration of membranes embedded with voltage-sensing domains," D. Krepkiy, M. Mihailescu, J. A. Freites, E. V. Schow, D. L. Worcerter, K. Gawrisch, D. J. Tobias, S. H. White, and K. J. Swartz, Nature 462, 473-479 (2009).
"Hydroxide anion at the air-water interface," C. J. Mundy, I.-F. W. Kuo, H.-S. Lee, M. E. Tuckerman, and D. J. Tobias, Chem. Phys. Lett. (Frontiers Article) 481, 2-8 (2009).
"Insertion of Transmembrane Helices by the Sec61 Translocon," S. Jaud, M. Fernandez-Vidal, I. Nilsson, N. M. Meindl-Beinker, N. Hubner, D. J. Tobias, G. von Heijne, and S. H. White, Proc. Natl. Acad. Sci. USA 106, 11588-11593 (2009).
"Experimental and Theoretical Characterization of Water Uptake on Self-Assembled Monolayers: Understanding the Interaction of Water with Atmospherically Relevant Surfaces," S. G. Moussa, T. M. McIntire, M. Szori, M. Roeselova, D. J. Tobias, R. L. Grimm, J. C. Hemminger, and B. J. Finlayson-Pitts, J. Phys. Chem. B 113, 2060-2069 (2009).
"Dynamics of Internal Water Molecules in Squid Rhodopsin," E. Jardon-Valadez, A. N. Bondar, and D. J. Tobias, Biophys. J. 96, 2572-2576 (2009).
"Hydration Dynamics of Purple Membranes," D. J. Tobias, N. Sengupta, and M. Tarek, Faraday Discuss. 141, 99-116 (2009).
"Hydration Dynamics in a Partially Denatured Ensemble of the Globular Protein Human Alpha-Lactalbumin Investigated with Molecular Dynamics Simulations," N. Sengupta, S. Jaud, and D. J. Tobias, Biophys. J. 95, 5257-5267 (2008).
"Getting Specific About Specific Ion Effects," D. J. Tobias and J. C. Hemminger, Science 319, 1197-1198 (2008).
"An Ab Initio Molecular Dynamics Study of the Solvated OHCl– Complex: Implications for the Atmospheric Oxidation of Chloride Ion to Molecular Chlorine," R. D'Auria, I.-F. W. Kuo, and D. J. Tobias, J. Phys. Chem. A 105, 4644-4650 (2008).
"Enhanced Photochemistry in Chloride-Nitrate Ion Mixtures," L. M. Wingen, A. C. Moskun, S. N. Johnson, J. L. Thomas, M. Roeselova, D. J. Tobias, D. J. Tobias, M. T. Kleinman, and B. J. Finlayson-Pitts, Phys. Chem. Chem. Phys. 10, 5668-5678 (2008).
"Coupling of Protein and Hydration-Water Dynamics in Biological Membranes," K. Wood, M. Plazanet, F. Gabel. B. Kessler, D. Oesterhelt, D. J. Tobias. G. Zaccai, and M. Weik, Proc. Natl. Acad. Sci. USA 104, 18049-18054 (2007).
"The Effect of an Organic Surfactant on the Liquid-Vapor Interface of an Electrolyte Solution," M. J. Krisch, R. D'Auria, M. A. Brown, D. J. Tobias, J. C. Hemminger, M. Ammann, D. E. Starr, and H. Bluhm, J. Phys. Chem. C 111, 13497-13509 (2007).
"Self-Induced Docking Site of a Deeply Embedded Peripheral Membrane Protein," S. Jaud, D. J. Tobias, J. J. Falke, and S. H. White, Biophys. J. 92, 517-524 (2007).
"Specific Ion Effects at the Air/Water Interface," P. Jungwirth and D. J. Tobias, Chem. Rev. 106, 1259-1281 (2006).
"A Voltage Sensor Water Pore" J. A. Freites, D. J. Tobias, and S. H. White, Biophys. J. 91, L90-L92 (2006).
"Interface Connections of a Transmembrane Voltage Sensor," J. A. Freites, D. J. Tobias, G. von Heijne, and S. H. White, Proc. Natl. Acad. Sci. USA 102, 15059-15064 (2005).
"Uptake and Collision Dynamics of Gas Phase Ozone at Unsaturated Organic Surfaces," J. Vieceli, O. L. Ma, and D. J. Tobias, J. Phys. Chem. A 108, 5806-5814 (2004).
"Molecular Dynamics Simulations of a Pulmonary Surfactant Protein B Peptide in a Lipid Monolayer," J. A. Freites, Y. Choi and D. J. Tobias, Biophys. J. 84, 2169-2180 (2003).
"Ions at the Air/Water Interface," P. Jungwirth and D. J. Tobias, J. Phys. Chem. B 106, 6361-6373 (2002).
"Role of Protein-Water Hydrogen Bond Dynamics in the Protein Dynamical Transition," M. Tarek and D. J. Tobias, Phys. Rev. Lett. 88, 138101 (2002).
"The Molecular Structure of Salt Solutions: A New View of the Interface with Implications for Heterogeneous Atmospheric Chemistry," P. Jungwirth and D. J. Tobias, J. Phys. Chem. B 105, 10468-10472 (2001).
"Experiments and Molecular/Kinetics Simulations of Ion-Enhanced Interfacial Chemistry on Aqueous NaCl Aerosols," E. Knipping, M. J. Lakin, P. Jungwirth, D. J. Tobias, R. B. Gerber, D. Dabdub, and B. J. Finlayson-Pitts, Science 288, 301-306 (2000).
Professional Societies
American Chemical Society
American Physical Society
American Association for the Advancement of Science
Biophysical Society
Research Centers
AirUCI Environmental Molecular Sciences Institute
Institute for Surface and Interface Science (ISIS)
Center for Biomembrane Systems
Institute for Genomics and Bioinformatics (IGB)
Center for Complex Bio Systems (CCBS)
Institute for Complex Adaptive Matter (ICAM)
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