Fig. 4
From: Genotype–phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders
Molecular modelling of identified PEX13 missense variants (p.Arg294Trp and p.Gly324Arg). A Analysis of 500 ns of atomistic molecular dynamics trajectories run in water solvent at 330 K, protein backbone RMSD for the wild type PEX13 (left), the mutant Gly324Arg (center), and its Glu294Trp mutant (right), running averages over 50 data points are highlighted (dark solid lines); B PEX13-wt:PEX14:PEX5 tetramer; C PEX13-Gly324Arg:PEX14:PEX5 tetramer; D PEX13-Arg294Trp:PEX14:PEX5 tetramer; E PEX13-wt:PEX13-WT homodimer; F PEX13-Arg294Trp:PEX13Arg294Trp homodimer; G–H solvent accessible surface area distribution of the residues responsible to the binding of PEX13 with PEX14 for PEX13-wt:PEX13-wt (G) and PEX13-Arg294Trp:PEX13-Arg294Trp (H), the distributions were calculated over both dimers of all configurations generated by docking, the monomers average value (dotted dashed lines) as well as its standard deviation (dashed lines) calculated over configurations sampled along 500 ns of molecular dynamics simulations are also indicated; I an aberrant PEX13-Arg294Trp:PEX13-Arg294Trp homodimers in which one of PEX14 binding site is buried due to dimerisation. Configurations were obtained by PEX13 homology modelling followed by 500 ns of molecular dynamics simulations and (B–D) docking to PEX14:PEX5 (E–I) blind docking to PEX13. The residues predicted to be involved in PEX13:PEX14 interactions (and selected binding site for the dockings of panels B–D) are highlighted (licorice), their solvent accessible surface area is labelled in panels E, F, I. Arg294 and Trp294 are highlighted in PEX13-wt and PEX13-Arg294Trp, respectively; Gly324 in PEX13-wt (B), and Arg324 in PEX13-Gly324Arg (C). Color code: PEX13-wt (green), PEX13-Gly324Arg (cyan), PEX13-Arg294Trp (magenta), PEX14 (white), PEX5 (blue)