Effect of Prestress on Epistasis in Elastic Network Models of Proteins

Elastic networks have been used to model allosteric function in proteins. Recently, these networks have also been used to chart the evolutionary pathways taking a network between two distinct functions. This is done by removing or replacing individual bonds in the network. Each such move is considered a mutation. One important aspect of mutations, captured by these systems, is that they are epistatic: the effect of a mutation depends on what other mutations have already taken place. The mechanics of epistasis have thus far only been investigated when all individual bond forces are zero. Here we extend the study to include prestress, the situation relevant for most materials and proteins, where individual springs are not at their rest length but each node is in force balance. We study the effect of prestress on epistasis and adaptability of function in a mechanical network relevant to proteins.