  The ability to absorb mutations while retaining structure and function, or
mutational robustness, is a remarkable property of natural proteins. In this
Letter, we use a computational model of organismic evolution [Zeldovich et al,
PLOS Comp Biol 3(7):e139 (2007)], which explicitly couples protein physics and
population dynamics, to study mutational robustness of evolved model proteins.
We find that dominant protein structures which evolved in the simulations are
highly designable ones, in accord with some of the earlier observations. Next,
we compare evolved sequences with the ones designed to fold into the same
dominant structures and having the same thermodynamic stability, and find that
evolved sequences are more robust against point mutations, being less likely to
be destabilized upon them. These results point to sequence evolution as an
important method of protein engineering if mutational robustness of the
artificially developed proteins is desired. On the biological side, mutational
robustness of proteins appears to be a natural consequence of the
mutation-selection evolutionary process.
