Fig 1.
Schematic representation of the workflow.
Table 1.
SIFT, PolyPhen, and PANTHER predictions for the impact of amino acid substitution on the ALOX5AP gene.
Table 2.
Analysis of disease-associated nsSNPs on ALOX5AP gene.
Table 3.
Investigation of the molecular mechanisms underlying pathogenicity.
Table 4.
Investigation of the molecular mechanisms underlying pathogenicity.
Fig 2.
ConSurf analysis for critical residues in ALOX5AP.
(A). ConSurf analysis results in terms of residue conservation and the 3D of the protein structure. A. The amount of confidence in the sequence conservation is shown by a range of colors in the ConSurf results. The sky-blue color in this color scheme stands for variable residues, while the dark purple color stands in for highly conserved residues. (B) 3D ALOX5AP indicated the position of the mutants within PDB ID 2Q7M, this figure is prepared using PyMOL [47].
Fig 3.
RMSD (A) and RMSF (B) analyses of ALOX5AP and its Variant proteins.
Comparative MD analyses of wildtype ALOX5AP and selected variants, showing (A) RMSD trajectories indicating overall protein stability, and (B) RMSF profiles highlighting residue-level flexibility differences (ALOX5AP wildtype in black, L12F in orange, A56V in green, G75R in blue, G87R in purple). The duration of MD simulation was 100 ns.
Fig 4.
Radius of gyration (Rg) Analyses of ALOX5AP wildtype and its Variants.
Comparative analysis of Rg trajectories for Cα atoms, depicting structural compactness and stability differences among wildtype ALOX5AP and mutant variants (ALOX5AP wildtype in black, L12F in orange, A56V in green, G75R in blue, G87R in purple) during MD simulations for 100 ns.
Fig 5.
SASA analyses of ALOX5AP wildtype and its variants.
SASA analyses of ALOX5AP wildtype and its variants for 100 ns. (ALOX5AP wildtype in black, L12F in orange, A56V in green, G75R in blue and G87R in purple).
Fig 6.
Hydrogen bond (HB) formation analyses of ALOX5AP wildtype and its variants.
HB formation analyses of ALOX5AP wildtype and its variant proteins for 100 ns (ALOX5AP wildtype in black, L12F in orange, A56V in green, G75R in blue and G87R in purple).
Fig 7.
Simulation trajectory snapshots of ALOX5AP wildtype and its variants.
Structural comparison of ALOX5AP wildtype and its Variant proteins based on simulation trajectory snapshots.