  Computational determination of the equilibrium state of heterogeneous
phospholipid mem-branes is a significant challenge. We wish to explore the rich
phase diagram of these multi-component systems. However, the diffusion and
mixing times in membranes are long com-pared to typical times of computer
simulations. To speed up the relaxation times, advanced simulation methods are
used. We evaluate the combination of enhanced sampling tech-niques such as MDAS
(Molecular Dynamics with Alchemical Steps) and MC-MD (Monte Carlo with
Molecular Dynamics) with a coarse-grained model of membranes (Martini) to
re-duce the number of steps and force evaluations that are needed to reach
equilibrium. We illustrate a significant gain compared to straightforward
Molecular Dynamics of the Martini model by factors between three to ten. The
combination is a useful tool to enhance the study of phase separation and the
formation of domains in biological membranes.
