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Jens Meiler

Title and Contact Information

Professor of Chemistry

Office: 5144B MRBIII
Phone: (615) 936-5662


Ph.D., University Frankfurt, 2001


Physical Chemistry
Computational Structural Biochemistry
Chemical Biology
Center for Structural Biology
Biophysical Chemistry

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Structural and Chemical Biology

Research in our laboratory seeks to fuse computational and experimental efforts to investigate proteins, the fundamental molecules of biology, and their interactions with small molecule substrates, therapeutics, or probes. We develop computational methods with three major ambitions in mind: 1) to enable protein structure elucidation of membrane proteins – the primary target of most therapeutics – and large macromolecular complexes such as viruses; 2) design proteins with novel structure and/or function to explore novel approaches to protein therapeutics and deepen our understanding of protein folding pathways, and 3) understand the relation between chemical structure and biological activity quantitatively in order to design more efficient and more specific drugs. Crucial for our success is the experimental validation of our computational approaches which we pursue in our laboratory or in collaboration with other scientists. For a complete list of research projects please visit

Current research projects include:

  1. Protein Structure Elucidation of EMRE.
    EmrE is a 12 kDa small multidrug resistant transporter (SMR) protein. It contributes to multidrug resistance in cancer and bacterial cells by removing compounds toxic to the cell such as the therapeutics. EmrE has been shown to contain four transmembrane α-helices and form a homodimer. While X-Ray crystallography and NMR spectroscopy frequently yield datasets for membrane proteins that are of lesser quality and/or sparse compared to soluble proteins, extensive Electron Paramagnetic Resonance (EPR) and cryo-Electron Microscopy (cryo-EM) datasets are available for EmrE. We develop computer algorithms tailored for determining the structure from these low resolution/sparse experimental data with the ultimate goal of solving the structure of EmrE and other membrane proteins. By determining the structure of EmrE, novel chemotherapeutic agents could be developed, including those to combat multidrug resistance.
    figure 1

  2. Design of Protein Antibiotics.
    Gram positive bacterial infections are a significant global cause of human mortality. More than 125,000 people contract multidrug-resistant gram positive infections annually in the U.S. alone, resulting in more than 40,000 deaths per year. Vancomycin is the last-line antibiotic for gram-positive infections. It kills bacteria by binding the -D-ala-D-ala C-terminus of a key bacterial cell wall glycopeptide component, thereby inhibiting proper cell wall biosynthesis. The most common mechanism of acquired resistance is through the substitution of a -D-lac in place of the -D-ala at the C-terminus of the bacterial glycopeptide. The goal of this project is to explore a rational design approach to develop novel antimicrobial protein therapeutics capable of binding both the multidrug-resistant -D-ala-D-ala and vancomycin-resistant -D-ala-D-lac target peptides.

  3. Novel Schizophrenia Therapeutics by Virtual High-Throughput Screening.
    Selective potentiators of the metabotropic glutamate receptor subtype mGluR5 have exciting potential for development of novel treatment strategies for schizophrenia. A high-throughput screen (HTS) for mGluR5 potentiators at Vanderbilt's molecular libraries screening center network facility revealed a large and diverse set of about 1,400 substances. We utilize the power of recent machine learning techniques such as Artificial Neural Networks (ANNs) and Support Vector Machines (SVMs) to model the complex relationship between chemical structure and biological activity of mGluR5 potentiators. These models will be used to virtually screen millions of compounds for activity and guide chemical synthesis of novel compounds.

Selected Publications

Martin EKnapp SEngh RAMoebitz HVarin TRoux BMeiler JBerdini VBaumann AVieth M. Perspective on computational and structural aspects of kinase discovery from IPK2014. Biochimica et Biophysica Acta. 2015, pii: S1570-9639(15)00096-5. [Epub ahead of print]

Kroncke BMVanoye CGMeiler JGeorge AL JrSanders CR. Personalized Biochemistry and Biophysics. Biochemistry. 2015. [Epub ahead of print]

Vortmeier G, DeLuca SH, Els-Heindl S, Chollet C, Scheidt HA, Beck-Sickinger AG, Meiler J, Huster D. Integrating solid-state NMR and computational modeling to investigate the structure and dynamics of membrane-associated ghrelin. PLo S One. 2015. 10(3):e0122444.

Swale DR, Sheehan JH, Banerjee S, Husni AS, Nguyen TT, Meiler J, Denton JS. Computational and Functional Analyses of a Small-Molecule Binding Site in ROMK. Biophysical Journal 2015, 108(5): 1094-103.

Heinze S, Putnam DK, Fischer AW, Kohlmann T, Weiner BE, Meiler J. CASP10-BCL::Fold efficiently samples topologies of large proteins. Proteins. 2015, 83(3):547-63.

Donahue JP, Levinson RT, Sheehan JH, Sutton L, Taylor HE, Meiler J, D'Aquila RT, Song C. Genetic analysis of the localization of APOBEC3F to human immunodeficiency virus type 1 virion cores. Journal of Virology. 2015, 89(4):2415-24.

Lössl P, Kölbel K, Tänzler D, Nannemann D, Ihling CH, Keller MV, Schneider M, Zaucke F, Meiler J, Sinz A. Analysis of nidogen-1/laminin γ1 interaction by cross-linking, mass spectrometry, and computational modeling reveals multiple binding modes. PLoS One. 2014, 9(11):e112886.

Weiner, B. E., Alexander, N., Akin, L. R., Woetzel, N., Karakas, M., Meiler, J. BCL::Fold-Protein topology determination from limited NMR restraints. Proteins. 2014, 82 (4): 587-95.

Gregory, K. J., Nguyen, E. D., Malosh, C., Mendenhall, J. L., Zic, J. Z., Bates, B. S., Noetzel, M. J., Squire, E. F., Turner, E. M., Rook, J. M., Emmitte, K. A., Stauffer, S. R., Lindsley, C. W., Meiler, J., Conn, P. J. Identification of Specific Ligand-Receptor Interactions That Govern Binding and Cooperativity of Diverse Modulators to a Common Metabotropic Glutamate Receptor 5 Allosteric Site. ACS Chemical Neuroscience. 2014, 0 (0): [Epub ahead of print].

Alexander, N. S., Preininger, A. M., Kaya, A. I., Stein, R. A., Hamm, H. E., Meiler, J. Energetic analysis of the rhodopsin-G-protein complex links the α5 helix to GDP release. Nature Structural & Molecular Biology. 2014, 21 (1): 56-63.

Leman, J. K., Mueller, R., Karakas, M., Woetzel, N., Meiler, J. Simultaneous prediction of protein secondary structure and transmembrane spans. Proteins-Structure Function and Bioinformatics. 2013, 81 (7): 1127-1140.

Gregory, K. J., Nguyen, E. D., Reiff, S. D., Squire, E. F., Stauffer, S. R., Lindsley, C. W., Meiler, J., Conn, P.J. Probing the Metabotropic Glutamate Receptor 5 (mGlu(5)) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a "Molecular Switch" in PAM Pharmacology. Molecular Pharmacology. 2013, 83 (5): 991-1006.

Willis, J. R., Briney, B. S., DeLuca, S. L., Crowe, J. E., Meiler, J. Human Germline Antibody Gene Segments Encode Polyspecific Antibodies. PLOS Computational Biology. 2013, 9 (4): 406-414.

Mueller, R., Dawson, E. S., Meiler, J., Rodriguez, A. L., Chauder, B. A., Bates, B. S., Felts, A. S., Lamb, J. P., Menon, U. N., Jadhav, S. B., Kane, A. S., Jones, C. K., Gregory, K. J., Niswender, C. M., Conn, P. J., Olsen, C. M., Winder, D. G., Emmitte, K. A., Lindsley, C. W. Discovery of 2-(2-Benzoxazoyl amino)-4-Aryl-5-Cyanopyrimidine as Negative Allosteric Modulators (NAMs) of Metabotropic Glutamate Receptor 5 (mGlu5): From an Artificial Neural Network Virtual Screen to an In Vivo Tool Compound. ChemMedChem. 2012, 7 (3): 406-414.

Sliwoski, G., Lowe, E. W., Butkiewicz, M., Meiler, J. BCL::EMAS - Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR. Molecules. 2012, 17 (8): 9971-9989.

Mueller, R., Dawson, E. S., Niswender, C. M., Butkiewicz, M., Hopkins, C. R., Weaver, C. D., Lindsley, C. W., Conn, P. J., Meiler, J. Iterative experimental and virtual high-throughput screening identifies metabotropic glutamate receptor subtype 4 positive allosteric modulators. Journal of Molecular Modeling. 2012, 18 (9): 4437-4446.

Eisenbeis, S., Proffitt, W., Coles, M., Truffault, V., Shanmugaratnam, S., Meiler, J., Hocker, B. Potential of Fragment Recombination for Rational Design of Proteins. Journal of The American Chemical Society. 2012, 134 (9): 4019-4022.

Lemmon, G., Kaufmann, K., Meiler, J. Prediction of HIV-1 Protease/Inhibitor Affinity using RosettaLigand. Chemical Biology & Drug Design. 2012, 79 (6): 888-896.

Lindert, S., Alexander, N., Wotzel, N., Karakas, M., Stewart, P. L., Meiler, J. EM-Fold: De Novo Atomic-Detail Protein Structure Determination from Medium-Resolution Density Maps. Structure. 2012, 20 (3): 464-478.

Henry, L. K., Iwamoto, H., Field, J. R., Kaufmann, K., Dawson, E. S., Jacobs, M. T., Adams, C., Felts, B., Zdravkovic, I., Armstrong, V., Combs, S., Solis, E., Rudnick, G., Noskov, S. Y., DeFelice, L. J., Meiler, J., Blakely, R. D. A Conserved Asparagine Residue in Transmembrane Segment 1 (TM1) of Serotonin Transporter Dictates Chloride-coupled Neurotransmitter Transport. Journal of Biological Chemistry. 2011, 286 (35): 30823-30836.

Koehler, J., Meiler, J. Expanding the utility of NMR restraints with paramagnetic compounds: Background and practical aspects. Progress in Nuclear Magnetic Resonance Spectroscopy. 2011, 59 (4): 360-389.

DeLuca, S., Dorr, B., Meiler, J. Design of Native-like Proteins through an Exposure-Dependent Environment Potential. Biochemistry. 2011, 50 (40): 8521-8528.

Fortenberry, C., Bowman, E. A., Proffitt, W., Dorr, B., Combs, S., Harp, J., Mizoue, L., Meiler, J. Exploring Symmetry as an Avenue to the Computational Design of Large Protein Domains. Journal of The American Chemical Society. 2011, 133 (45): 18026-18029.

Olmsted, I. R., Xiao, Y., Cho, M., Csordas, A. T., Sheehan, J. H., Meiler, J., Soh, H. T., Bornhop, D. J. Measurement of Aptamer-Protein Interactions with Back-Scattering Interferometry. Analytical Chemistry. 2011, 83 (23): 8867-8870.

Morin, A., Meiler, J., Mizoue, L. S. Computational design of protein-ligand interfaces: potential in therapeutic development. Trends in Biotechnology. 2011, 29 (4): 159-166.

Van Eps, N., Preininger, A. M., Alexander, N., Kaya A. I., Meier, S., Meiler, J., Hamm, H. E., Hubbell, W. L., Lindsley, C. W., Denton, J. S. RosettaEPR: An integrated tool for protein structure determination from sparse EPR data. Journal Of Structural Biology. 2011, 173 (3): 506-514.