Ab initio RNA folding

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure

Second Symposium on Chemical Evolution and the Origin of Life

Recent findings by NASA Exobiology investigators are reported. Scientific papers are presented in the following areas: cosmic evolution of biogenic compounds, prebiotic evolution (planetary and molecular), early evolution of life (biological and geochemical), evolution of advanced life, solar system exploration, and the Search for Extraterrestrial Intelligence (SETI)

Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Bioinorganic Chemistry

This book covers material that could be included in a one-quarter or one-semester course in bioinorganic chemistry for graduate students and advanced undergraduate students in chemistry or biochemistry. We believe that such a course should provide students with the background required to follow the research literature in the field. The topics were chosen to represent those areas of bioinorganic chemistry that are mature enough for textbook presentation. Although each chapter presents material at a more advanced level than that of bioinorganic textbooks published previously, the chapters are not specialized review articles. What we have attempted to do in each chapter is to teach the underlying principles of bioinorganic chemistry as well as outlining the state of knowledge in selected areas. We have chosen not to include abbreviated summaries of the inorganic chemistry, biochemistry, and spectroscopy that students may need as background in order to master the material presented. We instead assume that the instructor using this book will assign reading from relevant sources that is appropriate to the background of the students taking the course. For the convenience of the instructors, students, and other readers of this book, we have included an appendix that lists references to reviews of the research literature that we have found to be particularly useful in our courses on bioinorganic chemistry

Supramolecular hydrogels and discrete structures based on metal coordination and hydrogen bonding

PhD ThesisThe complexation of thiolated nucleosides and nucleobases with a range of group 11 metal ions (Au(I), Ag(I), Cu(I/II), was observed to lead to the formation of hydrogels by simple inversion tests. Atomic force and electron microscopy of the xerogels showed, in many cases, the presence of fibres with lengths in the micrometre range and above; this provided evidence for the formation of coordination polymers. This thesis is concerned with the preparation, characterisation and investigation of the physical properties, mainly photoluminescence and conductivity, of these coordination polymers. 2’-Deoxy-6-thioguanosine was successfully synthesised and characterized by UV, IR, Mass, 1H-NMR, and 13C-NMR spectroscopy. The formation of coordination polymers upon reaction of Au(I), Ag(I), and Cu(II) ions with 2’-deoxy-6-thioguanosine and 6-thioguanosine in aqueous media produced hydrogels with up to 97% water+methanol by mass. The Au-6-thioguanosine gel was studied in more detail because of the interest in gold thiolate polymers and the novel properties observed for Au(I)-6-thioguanosine. Fluorescence spectroscopy observed a strong yellow emission (λmax = 606 nm) which is not present in 6-thioguanosine nor in the Au(I) solutions. The optical absorption spectrum of the coordination polymer showed a band at (λmax = 360 nm) assigned to the HOMO-LUMO transition located mainly on the S-Au-S…chain of the polymer. An induced CD band associated with the Au-S chain and an enhancement of the CD signal at shorter wavelengths, for transitions associated with the ligand, suggested the polymer has a helical structure. Further evidence was provided by analysis of the X-ray scattering pattern of the xerogel and atomic force microscopy of single fibres deposited on silicon chips. The observation of long Au(I)-6-thioguanosine fibres and strong photoluminescence suggests some delocalisation of the states associated with the Au-S chains and the possibility of electronic conductivity. This was demonstrated upon oxidative doping of Au(I)-6-thioguanosine xerogels coated over platinum microband electrodes. Treatment with iodine vapour or ([Br(C6H4)3N]SbCl6) in anhydrous acetonitrile were found to result in linear current-voltage characteristics. The temperature dependence of the conductance showed Arrhenius behaviour (over range of temperature 223 to 323 K) with an activation energy of 94 kJ mol-1. V More complex structures based on Au(I)-6-thioguanosine polymers were observed upon synthesising the polymer in the presence of duplex DNA (from calf thymus). The templating of the polymer on DNA produces long, regular, and uniform fibres with a beads-on-a-string morphology. An unusual self-assembly of Au(I)-6-thioguanosine at flat Si surfaces upon simple drop-casting, with slow evaporation was also observed. AFM images of these films showed the formation of well-defined layers, but with each layer comprising long ribbons exceeding the maximum length of the AFM scan (~15 micrometres). Ag(I)-containing hydrogels formed by reactions with 6-thioguanine, 6-mercaptopurine, and 2-thiocytosine were prepared and characterised by AFM, TEM, XPS, X-Ray, FTIR, UV-Vis, and fluorescent spectroscopy. Au(I) 2-thiocytosine was also prepared, but this produced a discrete complex rather than a gel. AFM of the Ag(I) xerogels showed the formation of very long fibres and this was confirmed by TEM images. FTIR and X-ray diffraction studies suggested the metal coordination occurred via S atoms in all three gels. The Au(I) 2-thiocytosine was found to have strong luminescence (λmax 622 nm). A new Ag(I):6-thioethero nucleoside complex was prepared containing 6-methylmercaptopurine riboside (6-MMPR) which was shown by single crystal X-ray diffraction to unexpectedly feature coordination via N7 rather than the thioether sulfur atom. Cu(II) & Co(II):6-methylmercaptopurine(6-MMP) were also synthesised as new discrete complexes. The metals binding was studied by single crystal X-ray diffraction which showed that the binding sites were N3& N9 for Cu(II) ions, and N9 for Co(II) ion in the complexes.Iraqi Ministry of Higher Education and Scientific Researc

The 1st Symposium on Chemical Evolution and the Origin and Evolution of Life

This symposium provided an opportunity for all NASA Exobiology principal investigators to present their most recent research in a scientific meeting forum. Papers were presented in the following exobiology areas: extraterrestrial chemistry primitive earth, information transfer, solar system exploration, planetary protection, geological record, and early biological evolution