Design and chance in the self-assembly of macromolecules

The principles of self-assembly are described for naturally occurring macromolecules and for complex assemblies formed from simple synthetic constituents. Many biological molecules owe their function and specificity to their three-dimensional folds, and, in many cases, these folds are specified entirely by the sequence of the constituent amino acids or nucleic acids, and without the requirement for additional machinery to guide the formation of the structure. Thus sequence may often be sufficient to guide the assembly process, starting from denatured components having little or no folds, to the completion state with the stable, equilibrium fold that encompasses functional activity. Self-assembly of homopolymeric structures does not necessarily preserve symmetry, and some polymeric assemblies are organized so that their chemically identical subunits pack stably in geometrically non-equivalent ways. Self-assembly can also involve scaffolds that lack structure, as seen in the multi-enzyme assembly, the degradosome. The stable self-assembly of lipids into dynamic membraneous sheets is also described, and an example is shown in which a synthetic detergent can assemble into membrane layers.