Insertion of the Ca2+-Independent Phospholipase A2 into a Phospholipid Bilayer via Coarse-Grained and Atomistic Molecular Dynamics Simulations
Figure 3
Atomistic MD simulation of the catalytic domain of iPLA2 in a lipid bilayer.
(A) Cutaway view of the catalytic domain inserted into the lipid bilayers from a representative snapshot of the simulations. The protein is represented as gray ribbons. The lipid phosphate headgroups are shown as a pale brown surface. A blue section of the protein indicates the anchor region (residues 708–730), which shows significantly reduced H/D exchange when the enzyme is in the membrane. The active site Ser519 is shown in CPK representation. A yellow volume indicates a cavity at the entrance of the active-site, which may be employed for the lipid extraction. The inserted side chains of three anchoring residues, Pro714, Trp715, and Leu717, are shown in CPK representations in brown, gray, and pink. (B) Close-up caption of the cluster of hydrophobic residues (Pro711, Pro714, Trp715, Leu717, Val721, Phe722) that are interacting with the lipid membrane. A horizontal line was drawn to indicate the approximate position of phosphate groups. The protein side chains are colored according to their charges (green = polar; gray = hydrophobic; blue = positively charged; red = negatively charged). (C) Equilibration of hydrogen bond interactions between the protein and the lipid headgroups during a 60 ns AA-MD simulation. (D) Time series of the insertion angle in three 60 ns AA-MD simulations.