A Novel Grid-Based Molecular Dynamics Protocol to Shuffle Lipids in Heterogenious Membranes

Abstract

Biological membranes are complex structures that protect cells from the external world and host among the most important processes in living organisms. Computer simulations are among the best tools to investigate membranes, resulting in a substantial development of force fields and methods in the last decade for accurately model and simulate membranes. Due to the broad range of compositions and the variety of functionalities, the initial configuration of a membrane has a strong impact on the final results. Therefore, standard MD protocols suggest to replicate the simulation using membranes where initial lipid placement differ significantly. Many tools exist that can be used to generate initial configurations of very complex membranes at different level s of atomic resolution. However, most of these resources demand long preparation time and several “mouse clicks” through Graphical User Interfaces (GUI). Here, we introduce a method that has been developed to rapidly generate new membranes with shuffled lipids and to provide multiple initial configurations within a matter of minutes. The algorithm developed here uses a set of external grid based potentials which reduces clashes between atoms before shuffling the lipids, followed by several checking procedures that test the quality of generated membranes. We show the performance of this method on three different systems that encompass most used cases in the MD community: a nanodisc, a protein-embedded flat membrane, and a phase-separated ternary mixture. Analyses such as membrane thickness, interdigitation, area, and mass density show that the method can reliably generate bilayers with almost identical physico-chemical properties to the initial membrane. This method has been implemented in the latest version of VMD as “Membrane Mixer” and can be accessed via a user-friendly GUI interface.