Recoverin is a neuronal calcium sensor involved in vision adaptation
that reversibly associates with cellular membranes via its calcium-activated myristoyl
switch. While experimental evidence shows that the myristoyl group significantly
enhances membrane affinity of this protein, molecular details of the binding process
are still under debate. Here, we present results of extensive molecular dynamics
simulations of recoverin in the proximity of a phospholipid bilayer. We capture
multiple events of spontaneous membrane insertion of the myristoyl moiety and
confirm its critical role in the membrane binding. Moreover, we observe that the
binding strongly depends on the conformation of the N-terminal domain. We propose
that a suitable conformation of the N-terminal domain can be stabilized by the
disordered C-terminal segment or by binding of the target enzyme, i.e., rhodopsin
kinase. Finally, we find that the presence of negatively charged lipids in the bilayer
stabilizes a physiologically functional orientation of the membrane-bound recoverin.