Biological macromolecules explored by pattern recognition

Electron microscopy represents a very direct method for determining the structure of biological macromolecules, and complements both the well-established technique of X-ray crystallography (c.f. Blundell and Johnson, 1976) and the still in-its-infancy field of structure prediction (Kolata, 1986, Blundell et al., 1987). Our research has involved establishing a precise methodology based on computerised image analysis and pattern recognition to enhance the visibility of statistically significant structural features in electron images of isolated macromolecules. Our newly developed technique of angular reconstitution enables us to orient in three dimensions the commonly occurring projection forms of the macromolecules and thus perform a 3D reconstruction. In this paper, we describe the steps involved in determining the structure of a biological macromolecule by electron microscopy and image analysis, including pattern recognition and three dimensional reconstruction.