where N R is the number of replicas. The inner loss function is composed of three terms. The first one targets the density profiles. In this case, n T is the number of particle types in the system, n b is the number of bins, w t is an optional weight parameter, and the densities ρ t and ρ ref t are estimated at the bin centers z b . The second one targets the area per lipid (APL). A L is the mean APL, naively calculated from the simulations as 2LxLy N lipids , A ref L is the experimental value for the APL, and w A is another optional weight. The last term is a cubic constraint for the numerical range of the χl,m matrix elements, which prevent model parameters from diverging to unphysical values, avoiding unstable simulations. Here, ∆χ is the boundary value.