Aggregation and self-assembly in colloidal and biological systems

Nature has been ingenious in devising materials and devices to have specialised properties and to perform specific tasks in living matter. Not only must molecular building blocks be synthesised, they must also adopt the correct conformations and assemble themselves into functioning superstructures. At the same time, they must avoid interfering with all the other organisational processes occurring within the same space.Many tasks in living cells are performed by proteins. These molecules are chains of amino acids that fold into intricate structures dedicated to their particular function. Determining the structure is an important stage in unravelling a protein's function, and this is most often achieved by x-ray crystallography. To obtain a useful resolution it is necessary to purify the protein and grow defect-free crystals up to almost millimetre size. However, proteins have evolved to be difficult to crystallise, since aggregation of that sort would be deleterious to their function. Indeed, diseases like that of haemoglobin C arise from unwanted crystallisation. Accordingly, searching for physical conditions where adequate crystals can be grown is a difficult and time-consuming task.An important factor affecting the tendency of proteins to crystallise is the directionality of their interactions with each other due to the non-uniformity of their surfaces. Very little is known about the influence of directionality on crystallisation, and a major aim of the research proposed here is to investigate the effects using computer simulation. Although computer power continues to increase apace, it is nowhere near sufficient to treat an atom-by-atom representation of protein crystallisation. Instead of such a brute-force approach, we must devise coarse-grained models that embody the essential physics of protein interactions, and analyse them with sophisticated tools. In addition to being computationally tractable, these models have the advantage of revealing general underlying principles rather than case-specific answers.Proteins often organise themselves into discrete superstructures in order to accomplish a task. An elegant but pernicious example is the self-assembly of capsids, the coats of viruses that encapsulate their genetic material. About half of all viruses are roughly spherical (in fact, icosahedral) in shape, and are efficiently built from copies of a small number of proteins. The fact that many capsids can assemble reliably from their isolated subunits is remarkable and not easy to explain in detail. In particular, the ability to avoid construction errors and to form complete shells in favour of many partial fragments is poorly understood. Here again, simplified computer models can assist by elucidating possible pathways and the underlying thermodynamics of self-assembly. This knowledge could inspire antiviral therapy targeted at the assembly stage, rather than at infection itself. It could also be turned to positive uses by designing tiny containers to administer drugs.The coarse-grained modelling of biological molecules springs from techniques developed for colloid science. Colloids cover a broad range of dispersed nanoscale particles and everyday examples are as diverse as cream, ink and fog. In many human-made colloids, it is possible to exert fine control over the properties of the particles, thereby influencing their collective behaviour. Further projects in this proposal take up the idea of colloids as ``designer atoms.'' For example, how can rod-like molecules be encouraged to connect at low densities to make light-weight electrically conducting materials? What happens to colloidal gels and glassy materials if they are composed of mixtures of sizes and interactions rather than a uniform component? Computer simulations have a vital role to play in answering these questions.