PROTEIN DESIGN - A HIERARCHICAL APPROACH

The de novo design of peptides and proteins has recently emerged as an approach for investigating protein structure and function. Designed, helical peptides provide model systems for dissecting and quantifying the multiple interactions that stabilize secondary structure formation . De novo design is also useful for exploring the features that specif y the stoichiometry and stability of alpha-helical coiled coils and fo r defining the requirements for folding into structures that resemble native, functional proteins. The design process often occurs in a seri es of discrete steps. Such steps reflect the hierarchy of forces requi red for stabilizing tertiary structures, beginning with hydrophobic fo rces and adding more specific interactions as required to achieve a un ique, functional protein.