Michael F Brown

Michael F Brown

Professor, Applied Mathematics - GIDP
Professor, BIO5 Institute
Professor, Chemistry and Biochemistry-Sci
Primary Department
(520) 621-2163

Research Interest

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.


Perera, S. M., Chawla, U., & Brown, M. F. (2016). Powdered G-Protein–Coupled Receptors. Journal of Physical Chemistry Letters, 7, 4230-4235.
Brown, M. F., Salmon, A., Henriksson, U., & Söderman, O. (1990). Frequency Dependent 2H N.M.R. Relaxation Rates of Small Unilamellar Vesicles. Molecular Physics, 69, 379-383.
Merickel, M. B., Carman, C. S., Brookeman, J. R., III, J. M., Brown, M. F., & Ayers, C. R. (1988). Identification and 3-D quantification of atherosclerosis using magnetic resonance imaging. Computers in Biology and Medicine, 18(2), 89-102.

PMID: 3356147;Abstract:

Cardiovascular disease due to atherosclerosis is a leading cause of death in the United States as well as other developed countries. This paper describes the development of image processing, pattern recognition, and graphical display techniques to non-invasively quantify the atherosclerotic disease process using magnetic resonance imaging (MRI). We have demonstrated the ability to identify the soft tissue classes of (1) normal, smooth muscle wall, (2) fatty plaque, (3) complex, fibrous plaque, and (4) calcified plaque. The objective of this work hs been to combine functional information, such as plque tissue type, with structural information, represented by 3-D display of vessel structure, into a single composite display. The results of this work provide a 'high information content' display which will aid in the diagnosis and analysis of the atherosclerotic disease process, and permit detailed and quantitative studies to assess the effectiveness of therapies (e. g. changes in diet, exercise and drug administration).

Brown, M. F., Martínez-Mayorga, K., Nakanishi, K., F., G., & Struts, A. V. (2009). Retinal conformation and dynamics in activation of rhodopsin illuminated by solid-state 2H NMR spectroscopy. Photochemistry and Photobiology, 85(2), 442-453.

PMID: 19267870;PMCID: PMC2858981;Abstract:

Solid-state NMR spectroscopy gives a powerful avenue for investigating G protein-coupled receptors and other integral membrane proteins in a native-like environment. This article reviews the use of solid-state 2H NMR to study the retinal cofactor of rhodopsin in the dark state as well as the meta I and meta II photointermediates. Site-specific 2H NMR labels have been introduced into three regions (methyl groups) of retinal that are crucially important for the photochemical function of rhodopsin. Despite its phenomenal stability 2H NMR spectroscopy indicates retinal undergoes rapid fluctuations within the protein binding cavity. The spectral lineshapes reveal the methyl groups spin rapidly about their three-fold (C3) axes with an order parameter for the off-axial motion of For the dark state, the 2H NMR structure of 11-cis-retinal manifests torsional twisting of both the polyene chain and the β-ionone ring due to steric interactions of the ligand and the protein. Retinal is accommodated within the rhodopsin binding pocket with a negative pretwist about the C11=C12 double bond. Conformational distortion explains its rapid photochemistry and reveals the trajectory of the 11-cis to trans isomerization. In addition, 2H NMR has been applied to study the retinylidene dynamics in the dark and light-activated states. Upon isomerization there are drastic changes in the mobility of all three methyl groups. The relaxation data support an activation mechanism whereby the β-ionone ring of retinal stays in nearly the same environment, without a large displacement of the ligand. Interactions of the β-ionone ring and the retinylidene Schiff base with the protein transmit the force of the retinal isomerization. Solid-state 2H NMR thus provides information about the flow of energy that triggers changes in hydrogen-bonding networks and helix movements in the activation mechanism of the photoreceptor. © 2009 The Authors.

Brown, M. F. (2012). UV-visible and infrared methods for investigating lipid-rhodopsin membrane interactions. Methods in Molecular Biology, 914, 127–153.

We describe experimental UV-visible and Fourier transform infrared (FTIR) spectroscopic methods for characterizing lipid-protein interactions for rhodopsin in a membrane bilayer environment. The combination of FTIR and UV-visible difference spectroscopy is used to monitor the structural and functional changes during rhodopsin activation. Investigations of how membrane lipids stabilize various rhodopsin photoproducts are analogous to mutating the protein in terms of gain or loss of function. Interpretation of the results entails a flexible surface model for explaining membrane lipid-protein interactions through material properties relevant to biological activity.