The relationship between network structure/dynamics and biological function constitutes a fundamental issue in systems biology. However, despite many related investigations, the correspondence between structure and biological functions is not yet fully understood. A related subject that has deserved particular attention recently concerns how essentiality is related to the structure and dynamics of protein interactions. In the current work, protein essentiality is investigated in terms of long range influences in protein–protein interaction networks by considering simulated dynamical aspects. This analysis is performed with respect to outward activations, an approach which models the propagation of interactions between proteins by considering self-avoiding random walks. The obtained results are compared to protein local connectivity. Both the connectivity and the outward activations were found to be strongly related to protein essentiality.