Paths of long-range communication in the E2 enzymes of family 3: a molecular dynamics investigation

Molecular dynamics (MD) simulations have the ability to help reveal the relationship between protein structure, dynamics and function. Here, we describe MD simulations of the representative members of family 3 of E2 enzymes that we performed and analyzed with the aim of providing a quantitative description of the functional dynamics in this biologically important set of proteins. In particular, we combined a description of the protein as a network of interacting residues with the dynamical cross-correlation method to characterize the correlated motions observed in the simulations. This approach enabled us to detect communication between distal residues in these enzymes, and thus to reliably define all the likely intramolecular pathways of communication. We observed functionally relevant differences between the closed and open conformations of the enzyme, and identified the critical residues involved in the long-range communication paths. Our results highlight how molecular simulations can be used to aid in providing atomic-level details to communication paths within proteins.