Abstract
Theoretical studies of RNA and lattice protein models suggest that mutationally robust or the so‐called designable phenotypes tend to have special geometric features such as being more compact and more geometrically regular. Such geometrical forms have been also linked to speed of folding and stability properties that may also assist in promoting mutational robustness. Here we test these theoretical predictions on a non‐redundant collection of 2,660 experimentally determined structures from the PDB (Protein Data Bank) and CATH (Class Architecture Topology Homologous superfamily) database. We first developed an index summarizing the geometrical regularity of the structures and then used this index to show that the statistical pattern of empirical data is consistent with the theoretical predictions relating geometry to mutational robustness. Mutationally robust proteins tend to be more symmetric and compact. But, the relationship between compactness and robustness cannot be explained simply by the geometrical packing of individual amino acids in proteins; rather, it is the property of the whole system that is related to the statistical characteristics of the folding landscape. Finally, we hypothesize that a triplet relationship between mutational robustness, stability and form is a general properties of objects that optimize real‐valued relationships between sequences and discrete structures. J. Exp. Zool. (Mol. Dev. Evol.) 310B:216–226, 2008. © 2007 Wiley‐Liss, Inc.