Fig. 5: Predicted lipid occupancy for the outer leaflet phospholipid binding site.
a ELIC5 CA structure showing lipid density from a brief 20 ns equilibrium MD simulation to estimate expected thermal fluctuations of the glycerol backbone around the structurally-modeled POPG (pink licorice). The region of glycerol backbone density is shown in black, while the remaining lipid density is shown in pink. The five mutations of ELIC5 are shown in black licorice. b The SAFEP-calculated probability (pocc) that the structurally-identified site will be occupied by each of three possible lipids in a 2POPC:1POPE:xPOPG mixture, for both the WT CA conformation (top) and the ELIC5 CA conformation (bottom). c The predicted relative conformational stability \(\Delta {{\log }}\left(\frac{{p}_{{{\mbox{ELIC}}}5}}{{p}_{{{\mbox{WT}}}}}\right)\) as a function of mole fraction of POPG and POPE in a POPG:POPE:POPC mixture. Red and blue correspond to greater stability of the WT CA and ELIC5 CA conformations, respectively. White arrows indicate compositions where bulk calculations were carried out; remaining values were extrapolated as described in Methods. Data in panels b and c represent over 3 μs of simulation; pharmacological models relied on SAFEP-calculated parameters as described in Methods.
