Ensemble epistasis: thermodynamic origins of nonadditivity between mutations.

Abstract excerpt

Epistasis-when mutations combine nonadditively-is a profoundly important aspect of biology. It is often difficult to understand its mechanistic origins. Here, we show that epistasis can arise from the thermodynamic ensemble, or the set of interchanging conformations a protein adopts. Ensemble epistasis occurs because mutations can have different effects on different conformations of the same protein, leading to...

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