Michael F Brown
Professor, Applied Mathematics - GIDP
Professor, BIO5 Institute
Professor, Chemistry and Biochemistry-Sci
Primary Department
(520) 621-2163
Research Interest
Michael F. Brown is Professor of Chemistry & Biochemistry at the University of Arizona. He is co-director of the Biological Physics Program and the Chemical Physics Program, and was a co-founder of the Biological Chemistry Program at the University of Arizona. He is internationally renowned for his work on the molecular basis of activation of G-protein-coupled receptors that are the targets for the majority of pharmaceuticals and medicines used by humans. The focus of his work is on biomembranes, with a particular emphasis on lipid-protein interactions in relation to potential drug targets involving membrane proteins. He is involved with investigation of the molecular basis of visual signaling involving rhodopsin. Moreover, Professor Brown is an expert in nuclear magnetic resonance (NMR) spectroscopy. His activities in the area of biomolecular NMR spectroscopy involve the devolvement and application of methods for studying the structure and dynamics of biomolecules. Michael Brown has authored over 130 original research papers, 10 book chapters, 4 book reviews, and has published more than 275 abstracts. His current H-index is 43. He numbers among his coworkers various prominent scientists worldwide. He presents his work frequently at national and international conferences, and is the recipient of a number of major awards. Professor Brown's many contributions have established him as a major voice in the area of biomembrane research and biomolecular spectroscopy. He is frequently a member of various review panels and exerts an influence on science policy at the national level. Among his accolades, he is an elected Fellow of the American Association for the Advancement of Science; American Physical Society; Japan Society for the Promotion of Science; and the Biophysical Society. He is a Fellow of the Galileo Circle of the University of Arizona. Most recently, he received the Avanti Award of the Biophysical Society. This premier honor recognizes his vast and innovative contributions to the field of membrane biophysics, and groundbreaking work in the development of NMR techniques to characterize lipid structure and dynamics. Most recently he presented the 2014 Avanti lecture of the Biophysical Society.


Kobayashi, M., Struts, A. V., Fujiwara, T., Brown, M. F., & Akutsu, H. (2008). Fluid mechanical matching of H+-ATP synthase subunit c-ring with lipid membranes revealed by 2H solid-state NMR. Biophysical Journal, 94(11), 4339-4347.

PMID: 18310246;PMCID: PMC2480690;Abstract:

The F 1 F 0-ATP synthase utilizes the transmembrane H + gradient for the synthesis of ATP. F 0 subunit c-ring plays a key role in transporting H + through F 0 in the membrane. We investigated the interactions of Escherichia coli subunit c with dimyristoylphosphatidylcholine (DMPC-d 54) at lipid/protein ratios of 50:1 and 20:1 by means of 2H-solid-state NMR. In the liquid-crystalline state of DMPC, the 2H-NMR moment values and the order parameter (S CD) profile were little affected by the presence of subunit c, suggesting that the bilayer thickness in the liquid-crystalline state is matched to the transmembrane hydrophobic surface of subunit c. On the other hand, hydrophobic mismatch of subunit c with the lipid bilayer was observed in the gel state of DMPC. Moreover, the viscoelasticity represented by a square-law function of the 2H-NMR relaxation was also little influenced by subunit c in the fluid phase, in contrast with flexible nonionic detergents or rigid additives. Thus, the hydrophobic matching of the lipid bilayer to subunit c involves at least two factors, the hydrophobic length and the fluid mechanical property. These findings may be important for the torque generation in the rotary catalytic mechanism of the F 1F 0-ATPse molecular motor. © 2008 by the Biophysical Society.

Molugu, T. R., Leftin, A., Job, C., & Brown, M. F. (2014). Area Per Lipid of Membranes from Natural Abundance Solid-State 13C NMR Spectroscopy. Biophysical Journal, 106, 452a.
Vogel, A., Tan, K., Waldmann, H., Feller, S. E., Brown, M. F., & Huster, D. (2007). Flexibility of ras lipid modifications studied by 2H solid-state NMR and molecular dynamics simulations. Biophysical Journal, 93(8), 2697-2712.

PMID: 17557790;PMCID: PMC1989704;Abstract:

Human posttranslationally modified N-ras oncogenes are known to be implicated in numerous human cancers. Here, we applied a combination of experimental and computational techniques to determine structural and dynamical details of the lipid chain modifications of an N-ras heptapeptide in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes. Experimentally, 2H NMR spectroscopy was used to study oriented membranes that incorporated ras heptapeptides with two covalently attached perdeuterated hexadecyl chains. Atomistic molecular dynamics simulations of the same system were carried out over 100 ns including 60 DMPC and 4 ras molecules. Several structural and dynamical experimental parameters could be directly compared to the simulation. Experimental and simulated 2H NMR order parameters for the methylene groups of the ras lipid chains exhibited a systematic difference attributable to the absence of collective motions in the simulation and to geometrical effects. In contrast, experimental 2H NMR spin-lattice relaxation rates for Zeeman order were well reproduced in the simulation. The lack of slower collective motions in the simulation did not appreciably influence the relaxation rates at a Larmor frequency of 115.1 MHz. The experimental angular dependence of the 2H NM Rrelaxation rates with respect to the external magnetic field was also relatively well simulated. These relaxation rates showed a weak angular dependence, suggesting that the lipid modifications of ras are very flexible and highly mobile in agreement with the low order parameters. To quantify these results, the angular dependence of the 2H relaxation rates was calculated by an analytical model considering both molecular and collective motions. Peptide dynamics in the membrane could be modeled by an anisotropic diffusion tensor with principal values of D∥ = 2.1 × 109 s-1 and D⊥ = 4.5 × 105 s-1. A viscoelastic fitting parameter describing the membrane elasticity, viscosity, and temperature was found to be relatively similar for the ras peptide and the DMPC host matrix. Large motional amplitudes and relatively short correlation times facilitate mixing and dispersal with the lipid bilayer matrix, with implications for the role of the full-length ras protein in signal transduction and oncogenesis. © 2007 by the Biophysical Society.

Brown, M. F., & Rajamoorthi, K. (1991). Bilayers of Arachidonic Acid Containing Phospholipids Studied By 2H and 31P NMR Spectroscopy. Biochemistry, 30, 4204-4212.
Gibson, N. J., & Brown, M. F. (1990). Influence of pH on the MI-MII equilibrium of rhodopsin in recombinant membranes. Biochemical and Biophysical Research Communications, 169(3), 1028-1034.

PMID: 2363712;Abstract:

Rhodopsin in native rod membranes and incorporated into egg phosphatidylcholine (egg PC) vesicles was studied at pH 5 and 7 at 28°C. Rhodopsin function, as monitored by the formation of metarhodopsin II (MII) from metarhodopsin I (MI) following an actinic flash, was found to be largely blocked in egg PC vesicles at pH 7. When the pH was lowered to 5, however, rhodopsin showed essentially equal activity in both native and egg PC membranes. This activity exceeded that found for rhodopsin in native membranes at pH 7. Phospholipid composition is thus shown to directly affect the MI ⇌ MII equilibrium, which in turn is linked to visual function. © 1990.