个人简介

Ph.D. 1972, Columbia University

研究领域

Biophysical Chemistry: nucleic acid structure and function/RNA folding/therapeutics/and prediction of structure from sequence

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.

近期论文

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Condon, D.E., Yildirium, I., Kennedy, S.D., Mort, B.C., Kierzek, R., Turner, D.H., Gdaniec, Z., Kierzek, R. "Optimization of an AMBER Force Field for the Artificial Nucleic Acid, LNA, and Benchmarking with NMR of L(CAAU)," J. Phys. Chem. B. 2014, 118, 1216-1228. Dela-Moss, L.I., Moss, W.N., Turner, D.H. "Identification of Conserved RNA Secondary Structures at Influenza B and C Splice Sites Reveals Similarities and Differences between Influenza A, B, and C," BMC Research Notes 2014, 7:22. Kierzek, E., Malgowska, M., Lisowiec, J., Turner, D.H., Gdaniec, Z., Kierzek, R. "The Contribution of Pseudouridine to Stabilities and Structure of RNAs," Nucleic Acids Res. 2014, 42, 3492-3501. Turner, D.H. "Fundamental Interactions in RNA: Questions Answered and Remaining," Biopolymers 2013, 99, 1097-1104. Priore, S.F., Moss, W.N., Turner, D.H. "Influenza B Virus has Global Ordered RNA Structure in (+) and (-) Strands but Relatively Less Stable Predicted RNA Folding Free Energy than Allowed by the Encoded Protein Sequence," BMC Research Notes 2013, 6-330. Priore, S.F., Kierzek, E., Kierzek, R., Baman, J.R., Moss, W.N., Dela-Moss, L.I., Turner, D.H. "Secondary Structure of a Conserved Domain in the Intron of Influenza A NS1 mRNA," PLoS ONE 2013, 8(9), e70615. Tubbs, J.D., Condon, D.E., Kennedy, S.D., Hauser, M., Bevilacqua, P.C., Turner, D.H. "The Nuclear Magnetic Resonance of CCCC RNA Reveals a Right-Handed Helix, and Revised Parameters for AMBER Force Field Torsions Improve Predictions from Molecular Dynamics," Biochemistry 2013, 52, 996-1010. Kennedy, S.D., Kierzek, R., Turner, D.H. "Novel Conformation of an RNA Structural Switch," Biochemistry 2012, 51, 9257-9259. Morgado, C.A., Svozil, D., Turner, D.H., Sponer, J. "Understanding the Role of Base Stacking in Nucleic Acids. MD and QM Analysis of Tandem GA Pairs in RNA Duplexes," Physical Chemistry Chemical Physics 2012, 14, 12580-12591. Moss, W.N., Dela-Moss, L.I., Priore, S.F., Turner, D.H. "The Influenza A Segment 7 mRNA 3' Splice Site Pseudoknot/Hairpin Family," RNA Biology 2012, 9, 1305-1310. Moss, W.N., Dela-Moss, L.I., Kierzek, E., Kierzek, R., Priore, S.F., Turner, D.H. "The 3' Splice Site of Influenza A Segment 7 mRNA Can Exist in Two Conformations: A Pseudoknot and a Hairpin," PLoS ONE 2012, 7(6), e38323. Priore S.F., Moss W.N., Turner, D.H. "Influenza A Virus Coding Regions Exhibit Host-specific Global Ordered RNA Structure," PLoS ONE 2012, 7(4), e35989. Chen, J.L., Dishler, A.L., Kennedy, S.D., Yildirim, I., Liu, B., Turner, D.H., Serra, M.J. "Testing the Nearest Neighbor Model for Canonical RNA Base Pairs: Revision of GU Parameters," Biochemistry 2012, 51, 3509-3522. 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. 2012, 8, 172-181. 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. 2011, 7, 3779-3792. Moss, W. N., Eickbush, D. G., Lopez, M. J., Eickbush, T. H., Turner, D. H. "The R2 Retrotransposon RNA Families," RNA Biology 2011, 8, 714-718. 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 2011, 115, 9261-9270. 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. 2011, 286, 24872-24881. 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 2011, 17, 1664-1677. Moss, W. N., Priore, S. F., Turner, D. H. "Identification of Potential Conserved RNA Secondary Structure throughout Influenza A Coding Regions," RNA 2011, 17, 991-1011. 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 2011, 50, 640-653. 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 2010, 49, 5817-5827. 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 2010, 49, 5817-5827. 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. 2010, 6, 1520-1531. 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. 2010, 6, 910-929. Turner, D. H., Mathews, D. H. "NNDB: The Nearest Neighbor Parameter Database for Predicting Stability of Nucleic Acid Secondary Structure," Nucleic Acids Res. 2010, 38, D280-D282. Liu, B., Shankar, N., Turner, D. H. "Fluorescence Competition Assay Measurements of Free Energy Changes for RNA Pseudoknots," Biochemistry 2010, 49, 623-634. Liu, B., Mathews, D. H., Turner, D. H. "RNA Pseudoknots: Folding and Finding," f1000 Biology Reports 2010, 2, 8. Mathews, D. H., Moss, W. N., Turner, D. H. "Folding and Finding the RNA Secondary Structure," The RNA Worlds, 2010, 293-307, 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 2009, 48, 10822-10893. Shroeder, S. J., Turner, D. H. "Optical Melting Measurements of Nucleic Acid Thermodynamics," Methods in Enzymology 2009, 371-387, 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. 2009, 5, 2088-2100. 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. 2009, 390, 428-442. Chen, G., Kennedy, S.D., Turner, D.H. "A CA+ Pair Adjacent to a Sheared GA or AA Pair Stabilizes Size-Symmetric RNA Internal Loops," Biochemistry 2009, 48, 5738-5752. Kierzek, E., Pasternak, A., Pasternak, K., Gdaniec, Z., Yildirium, I., Turner, D.H., Kierzek, R. "Contributions of Stacking, Preorganization, and Hydrogen Bonding to the Thermodynamic Stability of Duplexes between RNA and 2'-O-methyl RNA with Locked Nucleic Acids (LNA)," Biochemistry 2009, 48, 4377-4387. 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. 2008, 130, 10233-10239. Pasternak, A., Kierzek, E., Pasternak, K., Fratczak, A., Turner, D.H., Kierzek, R. "The thermodynamics of 3'-terminal pyrene and guanosine for the design of isoenergetic 2'-O-methyl-RNA-LNA chimeric oligonucleotide probes of RNA structure," Biochemistry 2008, 47, 1249-1258. Kierzek, E., Kierzek, R., Moss, W.N., Christensen, S.M., Eickbush, T.H., Turner, D.H. "Isoenergetic Penta- and Hexanucleotide Microarray Probing and Chemical Mapping Provide a Secondary Structure Model for an RNA Element Orchestrating R2 Retrotransposon Protein Function," Nucleic Acids Res. 2008, 36, 1770-1782. Li, H., Liang, R., Turner, D.H., Rothberg, L.J., Duan, S. "Selective Nanoparticle Quenching of Fluorescence from Unbound Oligonucleotides as a Probe of RNA Structure," RNA 2007, 13, 2034-2041. Shankar, N., Xia, T., Kennedy, S.D., Krugh, T.R., Mathews, D.H., Turner, D.H. "NMR Reveals Absence of Hydrogen Bonding in Adjacent UU and AG Mismatches in an Isolates Interal Loop from Ribosomal RNA," Biochemistry 2007, 46, 12665-12678. Pasternak, A., Kierzek, E., Pasternak, K., Turner, D.H., Kierzek, R. "The Chemical Synthesis of 2'-O-methyk-2,6-diaminopurine Riboside and LNA-2,6-diaminopurine Riboside and their Influence on the thermodynamic Properties of 2'-O-methyl RNA/RNA Heteroduplexes," Nucleic Acids Res. 2007, 35, 4055-4063. 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 2007, 111, 6718-6727. Mathews, D.H., Turner, D.H., Zuker, M. "RNA Secondary Structure Prediction," Current Protocols in Nucleic Acid Chemistry 2007, Supplement 28, 11.2.1-11.2.17. Tolbert, B.S., Kennedy, S.D., Schroeder, S.J., Krugh, T.R., Turner, D.H. "The NMR Structures of (rGCUGAGGCU)2, and (rGCGGAUGCU)2: Probing the structural Features that Shape the Thermodynamic Stability of GA Pairs," Biochemistry 2007, 46, 1511-1522. Lu, Z.J., turner, D.H., Mathews, D.H. "A Set of Nearest Neighbor Parameters for Predicting the Enthalpy Change of RNA Secondary Structure Formation," Nucleic Acids Res. 2006, 34, 4912-4924. 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 2006, 45, 11776-11789. Duan, S., Mathews, D.H., Turner, D.H. "Interpreting Oligonucleotide Microarray Data to Determine RNA Secondary Structure: Application to the 3' End of Bombyx mori R2 RNA," Biochemistry 2006, 45, 9819-9832. Kierzek, E., Mathews, D.H., Ciesielska, A., Turner, D.H., Kierzek, R. "Nearest Neighbor Parameters for Watson-Crick Complementary Heteroduplexes Formed between 2'-O-methyl RNA and RNA Oligonucleotides," Nucleic Acids Res. 2006, 34, 3609-3614. Mathews, D.H., Turner, D.H. "Prediction of RNA Secondary Structure by Free Energy Minimization," Current Opinions in Structural Biology 2006, 16, 270-278. Jang, S.B., Hung, L-W., Jeong, M.S., Holbrook, E.L., Chen, X., Turner, D.H., Holbrook, S.R. "The Crystal Structure at 1.5 Å Resolution of an RNA Octamer Duplex Containing Tandem G-U Base Pairs," Biophysical J. 2006, 90, 4530-4537. Chen, G., Kennedy, S.D., Krugh, T.R., Turner, D.H. "An Alternating Sheared AA Pair and Elements of Stability for a Single Sheared Purine-Purine Pair Flanked by Sheared GA Pairs," Biochemistry 2006, 45, 6889-6903. Chen, G., Turner, D. H. "Consecutive GA Pairs Stabilize Medium-Size RNA Internal Loops," Biochemistry 2006, 45, 4025-4043. Kierzek, E., Kierzek, R., Turner, D.H., Catrina, I.E. "Facilitating RNA Structure Prediction with Microarrays," Biochemistry 2006, 45, 581-593. Mathews, D.H., Schroeder, S.J., Turner, D.H., Zuker, M. "Predicting RNA Secondary Structure," in The RNA World 2006, 3rd edition, ed. By R.F. Gesteland, T.R. Cech, J.F. Atkins, Cold Spring Harbor Press, 631-657. Yildirium, I., Turner, D.H. "RNA Challenges for Computational Chemists," Biochemistry 2005, 44, 13225-13234. Kierzek, E., Ciesielska, A., Pasternak, K., Mathews, D.H.,Turner, D.H., Kierzek, R. "The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes," Nucleic Acids Res. 2005, 33, 5082-5093. Chen, g., Znosko, B.M., Kennedy, S.D., Krugh, T.R., Turner, D.H. "Solution Structure of an RNA Internal Loop with Three Consecutive Sheared GA Pairs," Biochemistry 2005, 44, 2845-2856. Disney, M.D., Stephenson, R., Wright, T.W., Haidaris, C.G., Turner, D.H., Gigliotti, F. "Activity of Hoechst 33258 Against Pneumocystis carinii f. sp. muris, Candida albicans, and Candida dubliniensis," Antimicrobial Agents and Chemotherapy 2005, 49, 1326-1330.