Membrane Mixer: A Toolkit for Efficient Shuffling of Lipids in Heterogeneous Biological Membranes.

Abstract

Molecular dynamics (MD) simulations of biological membranes have achieved such levels of sophistication that are commonly used to predict unresolved structures and various properties of lipids and to substantiate experimental data. While achieving sufficient sampling of lipid dynamics remains a major challenge, a commonly used method to improve lipid sampling, e.g., in terms of specific interactions with membrane-associated proteins, is to randomize the initial arrangement of lipid constituents in multiple replicas of simulations, without changing the overall lipid composition of the membrane of interest. Here, we introduce a method that can rapidly generate multiple replicas of lipid bilayers with different spatial and conformational configurations for any given lipid composition. The underlying algorithm, which allows one to shuffle lipids at any desired level, relies on the application of an external potential, here referred to as the "carving potential", that removes clashes/entanglements before lipid positions are exchanged (shuffled), thereby minimizing the energy penalty due to abrupt lipid repositioning. The method is implemented as "Membrane Mixer Plugin (MMP) 1.0" in VMD, with a convenient graphical user interface that guides the user in setting various options and parameters. The plugin is fully automated and generates new membrane replicas more rapidly and conveniently than other analogous tools. The plugin and its capabilities introduced here can be extended to include additional features in future versions.