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arXiv · 0806.3772

Emergence of mutationally robust proteins in a microscopic model of evolution

Konstantin B. Zeldovich·Eugene I. Shakhnovich
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Abstract

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.

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Konstantin B. Zeldovich, Eugene I. Shakhnovich. 2008-06-23. Emergence of mutationally robust proteins in a microscopic model of evolution. https://arxiv.org/abs/0806.3772

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