Re-evaluating the "rules" of protein topology.

It is well known that the set of observed topological arrangements of secondary structures in globular proteins is highly limited. These limitations have been explained as the consequence of several rules of thumb including a strong preference for right-handed connections, against crossing loops and certain beta strand patterns. We present a critical evaluation of the power of these rules to distinguish known from possible topologies in a large set of two- and three-layer protein structures and determine that although these rules are still largely valid, an increasing number of exceptions can be found to many of them. The rules are then used to construct a generalised linear model for assessing the probability of occurrence of an arbitrary topology in the PDB. Application of the model to a large set of topologies generated during structure prediction showed that many had a similar probability of occurrence to known PDB folds.