A molecular structure is an essential source to identify ligand binding sites in orphan human cytochrome P450 4A22 (CYP4A22) that belongs to family 4, which is known to be involved in the regulation of blood pressure. Thus, a homology model has been constructed for CYP4A22 and refined by molecular dynamics simulation (MDS). Subsequently, molecular docking was performed with possible substrates, arachidonic acid (essential fatty acid, AA) and erythromycin (therapeutic drug, ERY). These complexes were also subjected to MDS, which helped in predicting the energetically favorable binding sites for these ligands. Putative substrate recognition sites (SRSs) of this protein provide highly hydrophobic binding pockets for the target ligands. A few key ligand binding residues identified in this study indicates that they could also play a major role in ligand-channeling (F122, L132 and C230). Furthermore, it appears that they might serve critical support for the catalytic reaction center (E321, F450, P449 and R455). Structural analysis of channels proposed that the conformational changes might have originated from the active site upon ligand binding and transferred to the rest of the protein via SRSs, which could thereby regulate the channels in CYP4A22. Most of our prediction results are supported by other research groups. In summary, the first molecular modeling study of CYP4A22 yields structural knowledge, which would be helpful to design structure-based-drugs and functional experiments for the target protein.
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