Estimating the number of protein folds.

A number of fundamental questions in structural biology concern the diversity of protein architectures (or folds). Here, we address two of them, the size of the universe of folds, and the distribution of sequence families among them, using an analysis based on a new and rigorous statistical sampling method. In particular we show that the number of known non-transmembrane protein folds is approximately one half of the total that exist, and that certain superfolds should exist, which accommodate dozens of non-homologous sequence families.