Reply to Zimmerman et al.: The space of single domain protein structures is continuous and highly connected

At the level of structurally significant relationships between proteins, the major conclusions of our article (1) were: protein structure space is continuous [where “one can link two arbitrarily selected structures, following a path of statistically significant similar structures”(1)] and highly connected. Zimmerman et al. (2) focus on average network path lengths and question these conclusions on the basis that the average shortest path is seven. In fact, seven is not the average shortest path, but the longest minimum path length between almost all protein structures (see ref. 1 and its Figs. 2B and 1B …