Douglas H. Turner

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Douglas "Doug" H. Turner is an American chemist and Professor of Chemistry at the University of Rochester.

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Douglas H. Turner
Turner Group.jpg
Group picture of Turner group members and alumni, with Doug at center, at Doug's 60th birthday celebration.
Website http://rna.chem.rochester.edu/

Early life

Turner grew up in Brooklyn, New York.

Education

Turner attended Harvard College, where he graduated cum laude in Chemistry and was commissioned as a Second Lieutenant in the U.S. Army. He did his graduate work in the Chemistry Departments of Columbia University and Brookhaven National Labs, where he worked with George Flynn and Norman Sutin to develop the Raman laser temperature jump method for measuring kinetics on a nanosecond time scale. During this period, he also spent three months in Anniston, Alabama taking the Officer's Basic Course of the Army's Chemical Corp. Deciding that he liked science more than war, he turned down the opportunity to continue as an active duty officer and went to the University of California at Berkeley to postdoc with Ignacio Tinoco, Jr. There, he invented fluorescence detected circular dichroism for measuring the optical activity of the fluorescent component of a solution.

Professional life and scientific achievements

In 1975, Turner joined the faculty of the Chemistry Department at the University of Rochester, where he is still a Professor. Turner was also lucky to be part of the academic family of Tom Cech (Nobel Prize in Chemistry, 1989) during 2 sabbatical years at the University of Colorado at Boulder. Turner has been unusually lucky with his own academic family of 8 postdocs, 49 students who have graduated with Ph.D.'s, and his other collaborators. Together, they have discovered many of the fundamental principles that determine RNA structure. [1] These principles, occasionally dubbed "Turner Rules", [2] are used in many RNA structure prediction algorithms. This has helped advance methods for predicting RNA structure from sequence, as well as RNA-RNA interactions: e.g. miRNA or siRNA target binding. Methods using the "Turner Rules" are widely used by biochemists and biologists. [3] [4] In his own lab, these methods were used to discover potentially medically important RNA structures in influenza virus [5] including an RNA pseudoknot that may play a role in regulating splicing at the Influenza A Segment 7 3' Splice Site.

Recently, Turner and collaborators have used Nuclear Magnetic Resonance and Molecular Dynamics simulations of short RNAs to test understanding of the sequence dependence of stacking interactions. [6] [7] Much remains to be discovered.

Papers coauthored by Turner have been cited over 18,000 times. The work has also been recognized by Sloan and Guggenheim Fellowships, election as a Fellow of the American Association for the Advancement of Science (AAAS), selection by the American Chemical Society as a Gordon Hammes Lecturer, continuous funding of an NIH grant from 1976 to 2019, and coauthorship of more than 250 papers. With Ryszard Kierzek from the Institute of Bioorganic Chemistry in Poznan, he shared the AAAS Poland-US Science Award in 2016.

Turner has also served the scientific community by often teaching the first year undergraduate Chemistry course and the graduate Biophysical Chemistry course, by being a member of several NIH Study Sections, the Advisory Board of the Institute of Bioorganic Chemistry in Poznan, and the editorial board of the Biophysical Journal. He also co-chaired a Nucleic Acids Gordon Conference.

Related Research Articles

Nucleic acid Class of large biomolecules essential to all known life

Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA.

Protein Biomolecule consisting of chains of amino acid residues

Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity.

Biophysics Study of biological systems using methods from the physical sciences

Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. Biophysical research shares significant overlap with biochemistry, molecular biology, physical chemistry, physiology, nanotechnology, bioengineering, computational biology, biomechanics, developmental biology and systems biology.

Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression, or are degradation intermediates derived from the breakdown of larger nucleic acid molecules.

Aptamer Oligonucleotide or peptide molecules that bind specific targets

Aptamers (APT-uh-murz) are short sequences of artificial DNA or RNA that bind a specific target molecule. Like antibodies, which are used for similar purposes in biotechnology and medicine, they can show strong binding to their target, with little or no off-target binding. To highlight how they are similar to and different from antibodies, aptamers are sometimes called “chemical antibodies.” Aptamers and antibodies can be used in many of the same tasks, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes.

Nucleoprotein Type of protein

Nucleoproteins are proteins conjugated with nucleic acids. Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.

Biomolecular structure 3D conformation of a biological sequence, like DNA, RNA, proteins

Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable domains of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University.

Nucleic acid structure prediction is a computational method to determine secondary and tertiary nucleic acid structure from its sequence. Secondary structure can be predicted from one or several nucleic acid sequences. Tertiary structure can be predicted from the sequence, or by comparative modeling.

Adriaan "Ad" Bax is a Dutch-American molecular biophysicist. He was born in the Netherlands and is the Chief of the Section on Biophysical NMR Spectroscopy at the National Institutes of Health. He is known for his work on the methodology of biomolecular NMR spectroscopy.

Nucleic acid design

Nucleic acid design is the process of generating a set of nucleic acid base sequences that will associate into a desired conformation. Nucleic acid design is central to the fields of DNA nanotechnology and DNA computing. It is necessary because there are many possible sequences of nucleic acid strands that will fold into a given secondary structure, but many of these sequences will have undesired additional interactions which must be avoided. In addition, there are many tertiary structure considerations which affect the choice of a secondary structure for a given design.

Experimental approaches of determining the structure of nucleic acids, such as RNA and DNA, can be largely classified into biophysical and biochemical methods. Biophysical methods use the fundamental physical properties of molecules for structure determination, including X-ray crystallography, NMR and cryo-EM. Biochemical methods exploit the chemical properties of nucleic acids using specific reagents and conditions to assay the structure of nucleic acids. Such methods may involve chemical probing with specific reagents, or rely on native or analogue chemistry. Different experimental approaches have unique merits and are suitable for different experimental purposes.

This is a list of notable computer programs that are used for nucleic acids simulations.

DNA nanotechnology The design and manufacture of artificial nucleic acid structures for technological uses

DNA nanotechnology is the design and manufacture of artificial nucleic acid structures for technological uses. In this field, nucleic acids are used as non-biological engineering materials for nanotechnology rather than as the carriers of genetic information in living cells. Researchers in the field have created static structures such as two- and three-dimensional crystal lattices, nanotubes, polyhedra, and arbitrary shapes, and functional devices such as molecular machines and DNA computers. The field is beginning to be used as a tool to solve basic science problems in structural biology and biophysics, including applications in X-ray crystallography and nuclear magnetic resonance spectroscopy of proteins to determine structures. Potential applications in molecular scale electronics and nanomedicine are also being investigated.

Nucleic acid secondary structure

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNAs and RNAs tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

Nucleic acid NMR is the use of nuclear magnetic resonance spectroscopy to obtain information about the structure and dynamics of nucleic acid molecules, such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA structures had been determined by NMR spectroscopy.

The 3' splice site of the influenza A virus segment 7 pre-mRNA can adopt two different types of RNA structure: a pseudoknot and a hairpin. This conformational switch is proposed to play a role in RNA alternative splicing and may influence the production of M1 and M2 proteins produced by splicing of this pre-mRNA.

Macromolecular assembly

The term macromolecular assembly (MA) refers to massive chemical structures such as viruses and non-biologic nanoparticles, cellular organelles and membranes and ribosomes, etc. that are complex mixtures of polypeptide, polynucleotide, polysaccharide or other polymeric macromolecules. They are generally of more than one of these types, and the mixtures are defined spatially, and with regard to their underlying chemical composition and structure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands of atoms held together by covalent bonds; they are often characterized by repeating units. Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term supramolecular assembly is more often applied in non-biologic contexts. MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions, and can be in either non-repeating structures, or in repeating linear, circular, spiral, or other patterns. The process by which MAs are formed has been termed molecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.

The ViennaRNA Package is a set of standalone programs and libraries used for prediction and analysis of RNA secondary structures. The source code for the package is distributed freely and compiled binaries are available for Linux, macOS and Windows platforms. The original paper has been cited over 2000 times.

References

  1. Turner, D H; N Sugimoto; S M Freier (1988). "RNA Structure Prediction". Annual Review of Biophysics and Biophysical Chemistry. 17 (1): 167–192. doi:10.1146/annurev.bb.17.060188.001123. ISSN   0883-9182. PMID   2456074.
  2. Turner, D. H.; Mathews, D. H. (2009). "NNDB: The nearest neighbor parameter database for predicting stability of nucleic acid secondary structure". Nucleic Acids Research. 38 (Database issue): D280–D282. doi:10.1093/nar/gkp892. PMC   2808915 . PMID   19880381.
  3. Dotu, I.; Lorenz, W. A.; Van Hentenryck, P.; Clote, P. (2009). "Computing folding pathways between RNA secondary structures". Nucleic Acids Research. 38 (5): 1711–1722. doi:10.1093/nar/gkp1054. PMC   2836545 . PMID   20044352.
  4. Seetin, M. G.; Mathews, D. H. (2012). "RNA Structure Prediction: An Overview of Methods". Bacterial Regulatory RNA. Methods in Molecular Biology. Vol. 905. pp. 99–122. doi:10.1007/978-1-61779-949-5_8. ISBN   978-1-61779-948-8. PMID   22736001.
  5. Moss, W. N.; Priore, S. F.; Turner, D. H. (2011). "Identification of potential conserved RNA secondary structure throughout influenza a coding regions". RNA. 17 (6): 991–1011. doi:10.1261/rna.2619511. PMC   3096049 . PMID   21536710.
  6. Condon, David E.; Kennedy, Scott D.; Mort, Brendan C.; Kierzek, Ryszard; Yildirim, Ilyas; Turner, Douglas H. (2015-06-09). "Stacking in RNA: NMR of Four Tetramers Benchmark Molecular Dynamics". Journal of Chemical Theory and Computation. 11 (6): 2729–2742. doi:10.1021/ct501025q. ISSN   1549-9618. PMC   4463549 . PMID   26082675.
  7. Zhao, Jianbo; Kennedy, Scott D.; Berger, Kyle D.; Turner, Douglas H. (2020-03-10). "Nuclear Magnetic Resonance of Single-Stranded RNAs and DNAs of CAAU and UCAAUC as Benchmarks for Molecular Dynamics Simulations". Journal of Chemical Theory and Computation. 16 (3): 1968–1984. doi:10.1021/acs.jctc.9b00912. ISSN   1549-9618. PMID   31904966. S2CID   210043354.