Anatomy of protein structures: Visualizing how a one-dimensional protein chain folds into a three-dimensional shape

Here, we depict the anatomy of protein structures in terms of the protein folding process. Via an iterative, top-down dissecting procedure, tertiary structures are spliced down to reveal their anatomy: first, to produce domains (defined by visual three-dimensional inspection criteria); then, hydrophobic folding units (HFU); and, at the end of a multilevel process, a set of building blocks. The resulting anatomy tree organization not only clearly depicts the organization of a one-dimensional polypeptide chain in three-dimensional space but also straightforwardly describes the most likely folding pathway(s). Comparison of the tree with the formation of the hydrophobic folding units through combinatorial assembly of the building blocks illustrates how the chain folds in a sequential or a complex folding pathway. Further, the tree points to the kinetics of the folding, whether the chain is a fast or a slow folder, and the probability of misfolding. Our ability to successfully dissect the protein into an anatomy tree illustrates that protein folding is a hierarchical process and further validates a building blocks protein folding model.