Bridge proteins as connectors in sequence space.

A bi- or multi-stable protein (with a degenerate native state) is a bridge sequence if it has at least two 1-error mutants that fold non-degenerately into at least two different structures among the sequence's multiple native-state structures, i.e., each mutant folds uniquely to a different structure. In other words, there is at least one connection to the core of each of the two or more neutral networks. In total, for sequences with chain length studied here (see Methods), there are sequences in the model sequence space, 6349 of which have non-degenerate () native states.