The free energy landscape for the penetration of cyclocurcumin derivatives inside the lipid bilayer was explored using the recently developed metadynamics-extended adaptive biasing force (meta-eABF) algorithm. As a collective variable z we chose the projection of the distance between the center of masses of the cyclocurcumin derivative and the membrane onto the zdirection of the cartesian space, i.e. the normal to the membrane bilayer, was used in all cases. The permeation pathway was sampled from 0<z<50 Å and starting with the Z/E-isomers positioned randomly in the water phase. The pathway was discretized in bins of 0.5 Å wide, where samples of the local force were accumulated along z. The potential of mean force was evaluated through integration of the average force, with an asymptotically unbiased estimator of the free energy. The sampling time amounts to 660 ns and was repeated in two replicas achieving a proper representation of the studied phenomena. Classical equilibrium MD simulations were also performed with the chromophores placed in the water bulk and following the same protocol as previously detailed. All the calculations have been performed using the NAMD code and analyzed using VMD and Colvar.