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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (173 K)Download as PowerPoint slideHighlights► Recent diverse studies into the evolution and design of symmetric protein architecture are converging into a novel ‘top-down’ approach to protein design. ► Top-down design efforts have produced simplified peptide ‘building blocks’ useful in the subsequent design of symmetric target architecture. ► Common formalism might be established to enable greater success in top-down design methodology.