Fig. 3: Identification and quantification of lipid insertions in GPCR MDs.
a Visual scheme of the algorithm used to find shallow and deep lipid insertions in GPCR simulations (left) and total count of individual lipid insertions across the dataset classified by duration and depth (right). Lipid molecules found inside any of the inner core receptor selections displayed (left) at least once during a simulation constitute individual lipid insertions. Lipids spending more than 20% of their total insertion time inside the smaller inner core selection (salmon) constitute ‘deep’ insertions, otherwise being considered ‘shallow’ insertions. Insertions are classified, according to their duration, as ultra-short (<20 ns), short (20–100 ns), medium (100–300 ns), and long (>300 ns). More information on lipid insertion detection and classification can be found in the ‘methods’ section. b Dataset-wide average lipid insertion frequency by receptor site, classified by surrounding TM helices and GPCR side (either Extracellular (EC) or Intracellular (IC)). Frequency values are displayed in two bar plots (centre) and in four visual schemes (right) where each grey circle represents a TM helix and each coloured oval an insertion frequency value. Frequencies for individual simulated systems are available in Supplementary Data 3 and 4. c Barplots representing insertions of lipid-like molecules (Supplementary Table 2) in static PDB structures (top) and the average recovery rate of these insertions in the corresponding simulations, classified by receptor and insertion sites (bottom). Results available in Supplementary Data 5. d Recovery of an experimental lipid insertion in an A2AR simulated system (PDB id: 6AQF, GPCRmd id: 754 [https://www.gpcrmd.org/view/754]), where a POPC lipid (licorice, orange) appears inserted in TM1-TM7 EC, the same spot as a previous static insertion produced by an oleic acid co-solved molecule (licorice, cyan). This insertion site is separated from the ligand binding site by residues L2677x31 and Y2717x35 (licorice, purple). Source data are provided in the Source Data file.
