Implementation of the LipIDens pipeline: assisted interpretation of lipid densities in membrane protein structures using simulations

Abstract Interpretation of lipid and lipid-like densities surrounding membrane protein structures solved by cryo-electron microscopy (cryo-EM) is challenging. We developed the LipIDens pipeline for assisted structural interpretation of lipid densities using molecular dynamics (MD) simulations. This protocol details how to establish coarse-grained (CG) simulations of membrane proteins in biomimetic membranes, test lipid interaction cut-offs, calculate lipid interactions and binding sites, assess the quality of derived kinetics, compare lipid poses with structural densities, rank site lipids and refine lipid poses using atomistic simulations. These data provide a platform for identifying the most probable lipid accounting for a lipid-like density, assisting the modelling and interpretation of membrane protein structures.