It is generally acknowledged that geometrical and conformational properties of biopolymers have an important effect on their biochemical behaviour. It is less easily recognized that these properties depend also on their macromolecular electronic characteristics.

The aim of this review is to demonstrate the significance of such macromolecular electronic effects. Particularly useful for this sake is the recently much developed concept of ‘molecular electrostatic potential’ (MEP) (Scrocco & Tomasi, 1973, 1978) by which is defined the electrostatic (Coulomb) potential created in the neighbouring space by the nuclear charges and the eletronic distribution of a molecule.

In recent years it has become clear that different pathways are involved in the process of removing lesions from DNA. In spite of a continuous surveillance of the genetic integrity by repair enzymes, quite often lesions are not eliminated before the portion of the genome where they have been inserted is used for DNA replication or transcription. Actually, the number of unexcised lesions a cell can tolerate without significantly losing its capacity to reproduce is surprising. As an example, human fibroblasts from certain patients with the genetic disease xeroderma pigmentosum (XP)† are virtually unable to excise pyrimidine dimers, the major DNA lesion produced by short-wavelength UV light.

Isomorphous replacement methods have been revolutionary in macromolecular structure research. This has been most clearly demonstrated in protein crystallography. Specific binding of heavy atoms to protein molecules in the crystalline state provides the necessary reference for the phase determination of each Bragg reflexion and opens the way to the direct structure determination to atomic resolution from X-ray diffraction.

Are isomorphous replacement methods applicable to the investigation of non-crystalline structures as well? And if so, would there be any reasonable advantage?

An answer has been given by neutron scattering. Macromolecular assemblies of nucleic acids, proteins and lipids are most easily studied in H2O /D2O mixtures, as the scattering density of the solvent can be adjusted to any of the chemically different partial structures (Stuhrmann, 1974).