Colloquium: Geometrical approach to protein folding: a tube picture

A framework is presented for understanding the common character of proteins. Proteins are linear chain molecules. However, the simple model of a polymer viewed as spheres tethered together does not account for many of the observed characteristics of protein structures. The authors show here that proteins may be regarded as tubes of nonzero thickness. This approach allows one to bridge the conventional compact polymer phase with a novel phase employed by Nature to house biomolecular structures. The continuum description of a tube (or a sheet) of arbitrary thickness entails using appropriately chosen many-body interactions rather than two-body interactions. The authors suggest that the structures of folded proteins are selected based on geometrical considerations and are poised at the edge of compaction, thus accounting for their versatility and flexibility. This approach also offers an explanation for why helices and sheets are the building blocks of protein structures.