Designing proteins from simple motifs: opportunities in Top-Down Symmetric Deconstruction

The purpose of this review is to describe the development of 'top-down' approaches to protein design. It will be argued that a diverse number of studies over the past decade, involving many investigators, and focused upon elucidating the role of symmetry in protein evolution and design, are converging into a novel top-down approach to protein design. Top-down design methodologies have successfully produced comparatively simple polypeptide 'building blocks' (typically comprising 40-60 amino acids) useful in generating complex protein architecture, and have produced compelling data in support of macro-evolutionary pathways of protein structure. Furthermore, a distillation of the experimental approaches utilized in such studies suggests the potential for method formalism, one that may accelerate future success in this field.