Positive allosteric modulators of lecithin: Cholesterol acyltransferase adjust the orientation of the membrane-binding domain and alter its spatial free energy profile
Fig 4
(A) The average distances between the relevant residues mapped as a distance matrix plot. Drug 2a is used as an example as the rest of the compounds induced a similar change. (B) The distance between the α-carbon atoms of M66 and I231 as a function of time in Drug-2a and Nodrug-2 simulations (Left). The average distances between the α-carbon atoms of M66 and I231 for all simulated systems (Right). (C) Snapshots from Drug-2a and Nodrug-2 simulation showing the maxima and minima of the detected conformational change. The proteins are rendered as cartoons and the marker residues’ α-carbons as red spheres. (D) The distance plot derived from the simulation where compound 2a was removed from the allosteric site after 800 ns (Left). Two simulation snapshots superimposed showing the orientation of the MBD domain before (0 ns; green) and after the removal of compound 2a (120 ns; blue) (Right).