From local to global changes in proteins: a network view

•Protein dynamics express in the variety of their folds and functions.•Fold and function reshuffle by global changes triggered by local modification.•A single mutation can be lethal because it has too large global effects.•Associated with a second site mutation, the effects are contained and productive.•Little local modifications are necessary if positioned strategically.

To fulfill the biological activities in living organisms, proteins are endowed with dynamics, robustness and adaptability. The three properties co-exist because they allow global changes in structure to arise from local perturbations (dynamics). Robustness refers to the ability of the protein to incur such changes without suffering loss of function; adaptability is the emergence of a new biological activity. Since loss of function may jeopardize the survival of the organism and lead to disease, adaptability may occur through the combination of two local perturbations that together rescue the initial function. The review highlights the relevancy of computational network analysis to understand how a local change produces global changes.