In our previous study, we showed that also atomistic systems containing cholesterol can suffer from temperature gradients due to nonconverged constraints. Two examples are the CHARMM36 force field with hydrogen mass repartitioning (HMR) and the CHARMM36 model with hydrogens modelled as virtual sites (VIS). To allow time steps of up to ∆t = 5 fs, both models constrain all bonds. Although these cholesterol models do not contain any coupled triangles, larger rings of five or six atoms are present (Figure , left).