Physical contributions to the determination of biological structure and function

Since the Second World War important advances have been made in the understanding of biological phenomena in terms of the detailed three-dimensional structure of the molecules involved and the way these molecules interact with each other. Physicists have made valuable contributions to these developments: firstly in the development of physical techniques for investigating biological structures and secondly in the application of physical concepts and ideas to an analysis of biological processes. The techniques with which this review is mainly concerned are electron microscopy and x-ray diffraction. The application of electron microscopy is illustrated by some recent studies on virus structure where, in the interpretation of the electron micrographs, the high degree of symmetry in the virus particle is used. Recent advances in x-ray techniques are illustrated by describing their use in the determination of protein and nucleic acid structures. In particular the use of isomorphous replacement and anomalous dispersion in single-crystal protein analysis and of Fourier synthesis and automatic refinement techniques in fibre analysis is discussed.

From an analysis of the conformations which have been determined for a number of macromolecules it has been possible to formulate some general principles describing the forces important in defining macromolecular conformation and interaction. Attempts to apply these principles to the prediction of the conformation of other macromolecules are discussed. Many biological structures consist of highly specific aggregates of macromolecules. For the protein coat of simple viruses, principles of efficient design have been formulated to account for the observed structures in terms of identical protein sub-units arranged in approximately equivalent positions.

Recent theories of the control of cellular function are particularly interesting to physicists. Here control appears to be exercised by feedback processes and amplification of the signal is achieved by utilizing the co-operative behaviour of structures constructed from identical sub-units in equivalent positions.

Perhaps the most remarkable contribution of physics to biology has been to emphasize the high degree of order and precision in biological systems. Although to some extent this may have been exaggerated, because many physical techniques are most powerful in dealing with ordered systems, it is very likely that, as for inanimate matter, the ordered state is more common in living things than macroscopic examination might suggest.