In this paper, a structure-function analysis of B-DNA self-fitting is reviewed in the light of recent oligonucleotide crystal structures. Their crystal packings provided a high-resolution view of B-DNA helices closely and specifically fitted by groove-backbone interaction, a natural and biologically relevant manner to assemble B-DNA helices. In revealing that new properties of the DNA molecule emerge during condensation, these crystallographic studies have pointed to the biological importance of DNA—DNA interactions.

Electrostatic effects play an essential role in specific molecular recognition and molecular assembly in many biologically important molecules. The specific electric field at the active site also regulates the catalytic reaction of a protein. Moreover, intramolecular or inter-subunit electrostatic interactions, such as saltbridges, hydrogen bonds, and charge-dipole interactions, are considered to work to stabilize protein molecules. Those electrostatic roles recently observed in proteins are reviewed with a description of the origins and principles of electrostatic forces, and analyses will be made using simple models to illuminate the physical basis.

It has become standard practice to compare new amino-acid and nucleotide sequences with existing ones in the rapidly growing sequence databases. This has led to the recurring identification of certain sequence patterns, usually corresponding to less than 300 amino-acids in length. Many of these identifiable sequence regions have been shown to fold up to form a ‘domain’ structure; they are often called protein ‘modules’ (see definitions below). Proteins that contain such modules are widely distributed in biology, but they are particularly common in extracellular proteins.

DNA supercoiling is a consequence of the double-stranded nature of DNA. When a linear DNA molecule is ligated into a covalently closed circle, the two strands become intertwined like the links of a chain, and will remain so unless one of the strands is broken. The number of times one strand is linked with the other is described by a fundamental property of DNA supercoiling, the linking number (Lk).

Implementation and regulation of the molecular mechanisms underlying biological processes is dependent on direct interactions between biological molecules. These interactions are characterised by specific binding between at least one molecule and another, and for binding to occur the molecules must be able to come close enough to each other to make contact. One of the partners in the interaction is invariably a macromolecule (e.g. protein or DNA) or an assembly of large size, such as a lipid bilayer. The interaction may take place with the partners in solution, or with at least one attached to a biological surface (e.g. a membrane) or a very large structure such as a chromosome. Where the partners are part of a membrane or other large structure then there must be a mechanism, such as lateral diffusion in the plane of the membrane, that permits them to come together close enough for interaction.

Macromolecular X-ray crystallography underpins the vigorous field of structural molecular biology having yielded many protein, nucleic acid and virus structures in fine detail. The understanding of the recognition by these macromolecules, as receptors, of their cognate ligands involves the detailed study of the structural chemistry of their molecular interactions. Also these structural details underpin the rational design of novel inhibitors in modern drug discovery in the pharmaceutical industry. Moreover, from such structures the functional details can be inferred, such as the biological chemistry of enzyme reactivity. There is then a vast number and range of types of biological macromolecules that potentially could be studied. The completion of the protein primary sequencing of the yeast genome, and the human genome sequencing project comprising some 105 proteins that is underway, raises expectations for equivalent three dimensional structural databases.

In the years that have passed since the publication of Wolfram Saenger's classic book on nucleic acid structure (Saenger, 1984), a considerable amount of new data has been accumulated on the range of conformations which can be adopted by DNA. Many unusual species have joined the DNA zoo, including new varieties of two, three and four stranded helices. Much has been learnt about intrinsic DNA curvature, dynamics and conformational transitions and many types of damaged or deformed DNA have been investigated. In this article, we will try to summarise this progress, pointing out the scope of the various experimental techniques used to study DNA structure, and, where possible, trying to discern the rules which govern the behaviour of this subtle macromolecule. The article is divided into six major sections which begin with a general discussion of DNA structure and then present successively, B-DNA, DNA deformations, A-DNA, Z-DNA and DNARNA hybrids. An extensive set of references is included and should serve the reader who wishes to delve into greater detai.

To proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2 as well as of one-electron O2 reductants such as These two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of , and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2 and the O2 reductants when phosphorylating respiration fails to do this job due to lack of ADP.

In particular, it is proposed that some increase in the H+ leak of mitochondrial membrane in State 4 lowers , stimulates O2 consumption and decreases the level of which otherwise accumulates and serves as one-electron O2 reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.

Growing interest in gene targeting drugs has inspired the development of a multitude of nucleic acid analogues, many of which feature substitutions in the phosphodiester moiety of the backbone (reviewed by Mesmaeker et al. 1995 and Nielsen, 1995). Peptide nucleic acid (PNA) is an example of a more radical redesign of DNA. The entire sugar-phosphate backbone is substituted by a chain of peptide-like N-(2-aminoethyl)glycine units so that an achiral and uncharged DNA-mimic is obtained (Fig. 1; Nielsen et al. 1991). The synthesis is based on standard peptide chemistry (Christensen et al. 1995) and has been automated. PNA can relatively easily be modified to include modifications of the backbone as well as of the bases (Hyrup & Nielsen, 1996). PNA is chemically stable and, in contrast to natural nucleic acids and peptides, PNA is expected to remain intact in living cells since it is not a substrate for natural hydrolytic enzymes and is not degraded by cell extracts (Demidov et al. 1994).

The passage of molecules and information across cell membranes is mediated largely by membrane-spanning proteins acting as channels, pumps, receptors and enzymes. These proteins perform many tasks: they control electrochemical gradients across the membrane, receive signals from the environment or from other cells, convert light energy into chemical signals, transport small molecules into and out of cells, and harness proton gradients to generate the energy consumed in metabolism. Indeed, of the estimated 50000–100000 genes in the human genome, fully 20–40 % are thought to encode integral membrane proteins. If one also includes membrane-associated proteins, which are attached to the membrane surface through fatty acyl chains or electrostatic interactions, this percentage is likely to be much higher.