Section 22.1.2.1.1. Uses of surface-area calculations

Interactions between molecules are most likely to be mediated by the properties of residues at their surfaces. Surfaces have figured prominently in functional interpretations of macromolecular structure. Which residues are most likely to interact with other molecules? What are their properties: charged, polar, or hydrophobic? What would be the estimated energy of interaction? How do the shapes and properties complement one another? Which surfaces are most conserved among a homologous family? At the centre of these questions that are often asked at the start of a structural interpretation lies the calculation of the molecular and/or accessible surfaces.

Surface-area calculations are used in two ways. Graphical surface representations help to obtain a quick intuitive understanding of potential molecular functions and interactions through visualization of the shape, charge distribution, polarity, or sequence conservation on the molecular surface (for example). Quantitative calculations of surface area are used en route to approximations of the free energy of interactions in binding complexes.

Part of this subject area was the topic of an excellent review by Richards (1985), to which the reader is referred for greater coverage of many of the methods of calculation. This review will attempt to incorporate more recent developments, particularly in the use of graphics, both realistic and schematic.