In 1962, Caspar and Klug introduced the concept of quasi-equivalence to explain the arrangement of proteins on the surface of icosahedral virus particles (Caspar and Klug, 1962). The concept was based on the analysis of electron micrographs of spherical virus particles. The stoichiometry of these particles indicated that there were more than 60 chemically identical proteins making up the viral protein coat. However, symmetry of point groups precludes more than 60 identical objects from occupying symmetrically equivalent sites about point. This was an architectural problem that had been faced by Buckminster Fuller in his design of icosahedral domes. Examination of his work aided Caspar and Klug in systematically identifying all possible arrangements of identical structural elements in quasi-equivalent positions about a viral interior. Although it is impossible to place more than 60 chemically identical proteins in symmetrically identical positions in a protein coat, multiples of 60 proteins can be arranged such that they are all in nearly identical environments. The concept thus postulated that proteins could be adaptable to a limited extent in order to carry out requisite functions.
Proteins, however, have proven more adaptable than Caspar and Klug initially postulated. Their original paper predicted that polyoma and the very similar SV-40 would have 420 proteins in their coats. The results of x-ray crystallography and electron microscopy that proved that polyoma had 360 proteins in its coat (Rayment et al., 1983; Baker et al., 1988) were initially resisted, and Caspar had difficulties convincing the referees of the work that the results were correct because they went against his original theory. The remarkable results of Harrison and co-workers (Liddington et al., 1991) that visualized the high resolution structure of SV-40 showed that the coat proteins were remarkably adaptable in conforming to the 6 distinctly non-equivalent positions that they take on in the virion.
Moving from the low resolution images of viruses that first hinted at the adaptability of proteins in forming assemblies, to the high resolution molecular models of proteins in viruses, in helical assemblies, in actin, in myosin, is a remarkable journey. Proteins have proven more clever than structural biologists, and possibly more adaptable.
The movement of portions of proteins, as part of a functional response or action, or in response to changes in solvent, counterions and other environmental conditions is equally interesting. Movement, whether the wide swing of tropomyosin in crystalline arrays that are 95% solvent, the cross-bridge motion of myosin, or the dynamic fluctuation of tryptophans in gramicidin, is in every way as important to protein function as protein structure.
Philosophically, motion implies adaptability and adaptability implies motion. Consequently, it is clear, that action by a protein implies its ability to take on different structures. Similarly, those early micrographs of icosahedral viruses implied that the structural proteins of these viruses were capable of movement in response to their environment.
In this conference, we seek to explore as deeply as possible the relationship between the adaptability and movement of proteins and their many functions. Chemically identical proteins may be in quasi-equivalent environments, or, perhaps, non-equivalent environments. How are the proteins designed totake on the multiple conformations that their functioning requires? What do we know about the evolutionary engineering of movement, of adaptability in proteins? And what must we know in order to design proteins with pre-determined ranges of movement?
It is clear that movement and adaptabililty are every bit as tied to function as structure. However, we know far less about the linkage of movement and function than we do about the link of structure and function. Here, we will strive to define the questions that need to be asked about movement and adaptability of proteins in the future. In that way we hope that this conference may define questions for the future in the same way that the Cold Spring Harbor conference of 1962 defined many of the questions about protein structure that have been asked - and answered - over the past 35 years.