Paper detail

Comment on "Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field"

We report here on the pitfalls of the simulation model introduced in the "Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field" [Journal of Chemical Theory and Computation 2018, 14, 11, 6050-6062]. This refined Martini model was reported to reproduce experimental phase diagrams for a ternary DOPC/DPPC/cholesterol mixture, including the coexistence of two liquid phases. However, we demonstrate that this coexistence only emerged due to an unfortunate choice of simulation parameters, which leads to poor energy conservation. Specifically, the constraints on the cholesterol model drained energy out from the membrane, resulting in two coexisting phases at drastically different temperatures. Using the simulation parameters recommended for the used cholesterol model, this artefact is eliminated, yet so is phase coexistence, i.e. experimental phase diagrams are no longer reproduced. It is important to highlight that the present comment was submitted to Chemical Theory and Computation. However, it was rejected without peer-review by the Editor-in-Chief, who stated that the journal "rarely publishes such material".