Douglas H. Turner

Douglas H. Turner

Professor of Chemistry

Ph.D. 1972, Columbia University

Biophysical Chemistry of RNA Folding and Therapeutics

The research in Professor Turner's group focuses on the forces directing nucleic acid chemistry, with particular emphasis on RNA folding. This chemistry is important for life and for design of therapeutics. Nevertheless, much of it is not well understood. Studies of the properties of short oligonucleotides and related computational studies provide insight into the interactions determining the sequence dependence of the structures, energetics, and dynamics of nucleic acids.

Insight into the structures of large RNAs are provided by experiments that provide: (1) NMR spectra and (2) chemical reactivity of individual nucleotides. This information is incorporated into computer programs to predict the secondary and three-dimensional structure of an RNA. The results from these studies are providing the foundation for a bioinformatics approach to develop deeper interpretations of the many nucleic acid sequences determined by the Human Genome Project and other sequencing efforts. Binding of RNA to oligonucleotides in a microarray is providing information to facilitate design of therapeutics to target RNA.

The solutions to these challenging problems require many different clues. The group therefore applies the methods of UV and NMR spectroscopies, thermodynamics, computational chemistry, oligonucleotide synthesis, chemical and microarray mapping of RNA structure, and rapid reaction kinetics. By combining the results obtained from these various techniques, it is often possible to deduce unifying concepts for the nucleic acid chemistry.

The goal of the Turner group is to predict RNA secondary and 3D structure from sequence.

Selected Publications

Yildirium, I., Kennedy, S. D., Stern, H. A., Hart, J. M., Kierzek, R., Turner, D. H.  "Revision of AMBER Torsional Parameters for RNA Improves Free Energy Predictions of Tetramer Duplexes with GC and iGiC Base Pairs,"  J. Chem. Theory, Comput.  20128172-181.
Van Nostrand, K., Kennedy, S. D., Turner, D. H., Mathews, D. H.   "Molecular Mechanics Investigation of an Adenine-Adenine Non-Canonical Pair Conformational Change,"  J. Chem. Theory, Comput.  201173779-3792.
Moss, W. N., Eickbush, D. G., Lopez, M. J., Eickbush, T. H., Turner, D. H.  "The R2 Retrotransposon RNA Families,"  RNA Biology  20118714-718.
Yildirium, I., Stern, H. A., Tubbs, J. D., Kennedy, S. D., Turner, D. H.  "Benchmarking AMBER Force Fields for RNA: Comparisons to NMR Spectra for Single-stranded r(GACC) are Improved by Revised χ Torsions,"  J. Phys. Chem. B  20111159261-9270.
Noble, E., Mathews, D. H., Chen, J. L., Turner, D. H., Takamoto, T., Kim, B.  "Biophysical analysis of influenza A virus RNA promoter at physiological temperatures,"  J. Biol. Chem.  201128624872-24881.
Lerman, Y., Kennedy, S. D., Shankar, N., Parisien, M., Major, F., Turner, D. H.  "NMR Structure of a 4X4 Nucleotide RNA Internal Loop from an R2 Retrotransposon: Identification of a Three Purine-Purine Sheared Pair Motif and Comparison to MC-SYM Predictions,"  RNA  2011171664-1677.
Moss, W. N., Priore, S. F., Turner, D. H.  "Identification of Potential Conserved RNA Secondary Structure throughout Influenza A Coding Regions,"  RNA  201117991-1011.
Liu, B., Diamond, J. M., Mathews, D. H., Turner, D. H.  "Fluorescence Competition and Optical Melting Measurements of RNA Three-Way Multibranch Loops Provide a Revised Model for Thermodynamic Parameters,"  Biochemistry  201150640-653.
Liang, R., Kierzek, E., Kierzek, R., Turner, D. H.  "Comparisons between Chemical Mapping and Binding to Isoenergetic Oligonucleotide Microarrays Reveal Unexpected Patterns of Binding to the Bacillus subtilis RNase P RNA Specificity Domain,"  Biochemistry  2010495817-5827.
Hammond, N. B., Tolbert, B. S., Kierzek, R., Turner, D. H., Kennedy, S. D.  "RNA Internal Loops with Tandem AG Pairs: The Structure of the 5’GAGU/3’UGAG Loop can be Dramatically Different from Others, Including 5’AAGU/3’UGAA,"  Biochemistry  2010495817-5827.
Yildirium, I., Stern, H. A., Kennedy, S. D., Tubbs, J. D., Turner, D. H.  "Re-parameterization of RNA χ Torsion Parameters for the AMBER Force Field and Comparison to NMR Spectra for Cytidine and Uridine,"  J. Chem. Theory, Comput.  201061520-1531.
Reblova, K., Strelcova, Z., Kulhanek, P., Besseova, I., Mathews, D. H., Van Nostrand, K., Yildirium, I., Turner, D. H., Sponer, J.  "An RNA Molecular Switch: Intrinsic Flexibility of 23S rRNA Helices 40 and 68 5’-UAA/5’-GAN Internal Loops Studied by Molecular Dynamics Methods,"  J. Chem. Theory, Comput.  20106910-929.
Turner, D. H., Mathews, D. H.  "NNDB: The Nearest Neighbor Parameter Database for Predicting Stability of Nucleic Acid Secondary Structure,"  Nucleic Acids Res.  201038D280-D282.
Liu, B., Shankar, N., Turner, D. H.  "Fluorescence Competition Assay Measurements of Free Energy Changes for RNA Pseudoknots,"  Biochemistry  201049623-634.
Liu, B., Mathews, D. H., Turner, D. H.  "RNA Pseudoknots: Folding and Finding,"  f1000 Biology Reports  201028.
Mathews, D. H., Moss, W. N., Turner, D. H.  "Folding and Finding the RNA Secondary Structure,"  The RNA Worlds2010293-307, ed. by Atkins, J. F., Gesteland, R. F., and T. R. Cech, Cold Spring Harbor Press.
Carlucci, M., Kierzek, E., Olejnik, A., Turner, D. H., Kierzek, R.  "The Chemical Synthesis of LNA-2-thiouridine and it’s Influence on Stability and Selectivity of Oligonucleotide Binding to RNA,"  Biochemistry  20094810822-10893.
Shroeder, S. J., Turner, D. H.  "Optical Melting Measurements of Nucleic Acid Thermodynamics,"  Methods in Enzymology  2009371-387, ed. by D. Herschlag, Academic Press, Burlington.
Yildirim, I., Stern, H. A., Sponer, J., Spackova, N., Turner, D. H.  "Effects of Restrained Sampling Space and Nonplanar Amino Groups on Free-energy Predictions for RNA with Imino and Sheared Tandem GA Base Pairs Flanked by GC, CG, iGiC, or iCiG Base Pairs,"  J. Chem. Theory, Comput.  200952088-2100.
Kierzek, E., Christensen, S. M., Eickbush, T. H., Kierzek, R., Turner, D. H., Moss, W. N.  "Secondary Structures for 5' Regions of R2 Retrotransposon RNAs Reveal a Novel Conserved Pseudoknot and Regions that Evolve under Different Constraints,"  J. Mol. Biol.  2009390428-442.
Hart, J. M., Kennedy, S. D., Mathews, D. H., Turner, D. H.  "NMR-Assisted Prediction of RNA Secondary Structure: Identification of a Probable Pseudoknot in the Coding Region of an R2 Retrotransposon,"  J. Am. Chem. Soc.  200813010233-10239.
Chen, G., Kierzek, R., Yildirim, I., Krugh, T. R., Turner, D. H., Kennedy, S. D.  "Stacking Effects on Local Structure in RNA: The Structure of Tandem GA Pairs Changes When Flanking GC Pairs are Replaced by isoG-isoC Pairs,"  J. Phys. Chem. B  20071116718-6727.
Shankar, N., Kennedy, S. D., Chen, G., Krugh, T. R., Turner, D. H.  "The NMR Structure of an Internal Loop from 23S Ribosomal RNA Differs from its Structure in Crystals of 50S Ribosomal Subunits,"  Biochemistry  20064511776-11789.
Chen, G., Turner, D. H.  "Consecutive GA Pairs Stabilize Medium-Size RNA Internal Loops,"  Biochemistry  2006454025-4043.
Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M., Turner, D. H.  "Incorporating Chemical Modification Constraints into a Dynamic Programming Algorithm for Prediction of RNA Secondary Structure,"  Proc. Natl. Acad. Sci. U.S.A.  20041017287-7292.
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Professor Turner's Contact Information...

Office: Hutchison B08
Phone: (585) 275-3207

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