Concerted regulation of npc2 binding to endosomal/lysosomal membranes by bis(monoacylglycero)phosphate and sphingomyelin
Fig 2
The collective variables and the sampling approach.
npc2 structure overlaid with vectors showing the long (A) and the short (B) axes of the protein and the collective variables θ (A) and ϕ (B). The membrane normal defined as the vector between the com of P atoms of the upper and the lower leaflets of the membrane is represented with a solid arrow. A) The long axis is defined as a vector connecting the Cα com of residues 1–6, 19–38, 55–69, 93–109, 123–130 (pink), and that of residues 7–18, 39–54, 70–92, 110–122 (blue). B) The short axis is defined as a vector connecting the Cα com of residues 1–6, 13–45, 75–94, 124–130 (pink), and and that of residues 7–12, 46–74, 95–123 (blue). C) A schematic representation of the sampling approach. The numbers indicate the replica indices (i). Three separate wt-mtd simulations biasing |z| (i = 0, 3, …), θ (i = 1, 4, …), and ϕ (i = 2, 5, …) were performed within each window (w, shown in different colors) flanked by half harmonic restraints. Bias exchanges were attempted between simulations i and i + 1 in even (solid arrows) and odd pairings (dashed arrows). For a detailed discussion of the sampling procedure, see S1 Text.