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

TL;DR

This paper critiques a refined Martini coarse-grained force field model for lipid mixtures, revealing that its reported phase coexistence results were artifacts caused by simulation parameter choices, not actual physical behavior.

Contribution

It identifies the impact of simulation parameters on phase behavior results in coarse-grained lipid models, challenging previous claims of accurate phase diagram reproduction.

Findings

Incorrect phase coexistence due to poor energy conservation

Proper simulation parameters eliminate the observed phase coexistence

Experimental phase diagrams are not reproduced with correct parameters

Abstract

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".