The University of Wisconsin Genetics Computer Group (UWGCG) has been organized to develop computational tools for the analysis and publication of biological sequence data. A group of programs that will interact with each other has been developed for the Digital Equipment Corporation VAX computer using the VMS operating system. The programs available and the conditions for transfer are described.

/pdf/a-comprehensive-set-of-sequence-analysis-programs-for-the-luj6w12mfm.pdf

A comprehensive set of sequence analysis programs for the VAX

New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning.

The interaction of light within tissue has been used to recognize disease since the mid-1800s. The recent developments of small light sources, detectors, and fiber optic probes provide opportunities to quantitatively measure these interactions, which yield information for diagnosis at the biochemical, structural, or (patho)physiological level within intact tissues. However, because of the strong scattering properties of tissues, the reemitted optical signal is often influenced by changes in biochemistry (as detected by these spectroscopic approaches) and by physiological and pathophysiological changes in tissue scattering. One challenge of biomedical optics is to uncouple the signals influenced by biochemistry, which themselves provide specificity for identifying diseased states, from those influenced by tissue scattering, which are typically unspecific to a pathology. In this review, we describe optical interactions pursued for biomedical applications (fluorescence, fluorescence lifetime, phosphorescence, and Raman from cells, cultures, and tissues) and then provide a descriptive framework for light interaction based upon tissue absorption and scattering properties. Finally, we review important endogenous and exogenous biological chromophores and describe current work to employ these signals for detection and diagnosis of disease.

Quantitative optical spectroscopy for tissue diagnosis

The Cambridge Crystallographic Data Centre (CCDC) was established in 1965 to record numerical, chemical and bibliographic data relating to published organic and metal–organic crystal structures. The Cambridge Structural Database (CSD) now stores data for nearly 700 000 structures and is a comprehensive and fully retrospective historical archive of small-molecule crystallography. Nearly 40 000 new structures are added each year. As X-ray crystallography celebrates its centenary as a subject, and the CCDC approaches its own 50th year, this article traces the origins of the CCDC as a publicly funded organization and its onward development into a self-financing charitable institution. Principally, however, we describe the growth of the CSD and its extensive associated software system, and summarize its impact and value as a basis for research in structural chemistry, materials science and the life sciences, including drug discovery and drug development. Finally, the article considers the CCDC’s funding model in relation to open access and open data paradigms.

/pdf/the-cambridge-structural-database-in-retrospect-and-prospect-4nbzw83405.pdf

The Cambridge Structural Database in retrospect and prospect.

The present paper review the drug-DNA interactions, their types and applications of experimental techniques used to study interactions between DNA and small ligand molecules that are potentially of pharmaceutical interest. DNA has been known to be the cellular target for many cytotoxic anticancer agents for several decades. Understanding how drug molecules interact with DNA has become an active research area at the interface between chemistry, molecular biology and medicine. In this review article, we attempt to bring together topics that cover the breadth of this large area of research. The interaction of drugs with DNA is a significant feature in pharmacology and plays a vital role in the determination of the mechanisms of drug action and designing of more efficient and specifically targeted drugs with lesser side effects. Several instrumental techniques are used to study such interactions. In the present review, we will discuss UV-Visible spectroscopy, fluorescence spectroscopy and cyclic voltammetry. The applications of spectroscopic techniques are reviewed and we have discussed the type of information (qualitative or quantitative) that can be obtained from the use of each technique. Not only have novel techniques been applied to study drug-DNA interactions but such interactions may also be the basis for the development of new assays. The interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases.

Drug-DNA interactions and their study by UV-Visible, fluorescence spectroscopies and cyclic voltametry.

DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin.

Writing a review gives authors a splendid opportunity to view developments in a particular area of science from a very personal angle. They are at liberty to select material, emphasize aspects of direct interest to their own work and air speculations which, wisely or not, referees have caused to have removed from their publications. Such personal accounts often make good reading, but may be somewhat misleading especially for readers seeking an introduction to the field. One remedy is to aim at a comprehensive review with equal weight given to all publications but boredom, if not bias, is then likely to creep in.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500002997

Oligonucleotide structure: a decade of results from single crystal X-ray diffraction studies

The three-dimensional structure of the hydrated disodium salt of adenosine triphosphate (Na 2 ATP) has been determined from an X-ray diffraction study to a resolution of 0.9 A. The crystals are orthorhombic, space group P 2 1 2 1 2 1 , with a = 30.45(4), b = 20.88(3), c = 7.07(1) A. There are two molecules of ATP, four sodium ions, and six water molecules in the asymmetric unit. The structure was solved by direct methods and refined to R = 12.3 % using 1118 intensities measured on an automatic diffractometer. The triphosphate chain is in the folded conformation in each of the two crystallographically independent molecules. However, in one molecule (A) it is folded so as to form part of a lefthanded helix, while in the other part of a right-handed helix. There are corresponding differences in the conformations of the ribose rings. The ring is in the envelope conformation with C39 endo in molecule A and C29 endo in molecule B. Two of the sodium ions coordinate the two molecules through the phosphate oxygens and N7 to form an almost centrosymmetric ‘dimer’ which is the fundamental structural unit. The adenine bases show considerable overlap and are stacked in the c axis direction. Details of the hydrogen bonding and the role of water molecules in the structure are discussed.

The Crystal and Molecular Structure of Adenosine Triphosphate

We have employed a combination of temperature-dependent UV absorption spectroscopy, circular dichroism, and batch calorimetry to characterize the binding of actinomycin D to a series of oligomeric DNA duplexes. We find the duplex [d(CGTCGACG)]2 to be unique in its ability to bind actinomycin D strongly despite the absence of a classic GpC site. We present evidence that this non-GpC-containing duplex binds two actinomycin D molecules in an apparently cooperative manner to form a complex that exhibits aberrant spectroscopic and calorimetric behavior. We propose that these observations are consistent with actinomycin D exhibiting a high-affinity, sequence-dependent DNA-binding mode distinct from its classic binding to isolated GpC sites.

http://www.pnas.org/content/86/11/3968.full.pdf

Binding of actinomycin D to DNA: evidence for a nonclassical high-affinity binding mode that does not require GpC sites.

It is well known that DNA can exist in a variety of conformations which can be interconverted by relatively mild changes in conditions. The in vivo conformation of DNA is usually thought to be the B form, but there is recent evidence that other conforma-tions may be important in DNA–protein recognition. Different fragments of DNA crystallized under virtually identical conditions can form A, B or Z helices1. A fragment that adopted an A conformation in a crystal was found in the B conformation in solution2, whereas NMR spectroscopy of A-DNA films3 revealed the presence of a substantial amount of disordered B-DNA. Until now, however, a DNA fragment of a given sequence has not been crystallized in more than one global conformation4,5. We report here an X-ray diffraction study of crystals of the DNA octamer dGGBrUABrUACC. In addition to a 'framework' of A-DNA, which gives discrete X-ray reflections, there are partially disordered B-DNA helices, recognized by their diffuse scattering features.

Olga Kennard

Papers

DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin.

Oligonucleotide structure: a decade of results from single crystal X-ray diffraction studies

The Crystal and Molecular Structure of Adenosine Triphosphate

Binding of actinomycin D to DNA: evidence for a nonclassical high-affinity binding mode that does not require GpC sites.

Coexistence of A- and B-form DNA in a single crystal lattice.