Evaluation of binding affinities of anacardic acid and D-12 molecules in the active site of p300 HAT enzyme from Molecular docking and Molecular dynamics simulation analysis

Abstract

Abstract The p300 is a HAT family enzyme it regulates the transcription process in the eukaryotic cell nucleus. The irregular function of this enzyme is leads to cancer, cardiovascular and neurological disorders; needs a potential drug molecule for inhibition. The anacardic acid and D-12 molecules are potential inhibitor of p300 HAT enzyme with long tail in the structure. Even though, the detailed intermolecular interactions and stability of the molecules with p300 HAT enzyme are not explained in detail. The molecular docking analysis confirms D-12 [-14.1 kcal/mol] molecule gives the high docking score compared than the anacardic acid [-12.5 kcal/mol]. Both the molecules form an intermolecular interaction with catalytic site amino acid residues (Trp1436 and Tyr1467) of p300 HAT enzyme; in which, D-12 forms strong intermolecular interactions and it is stable during the MD simulation. During the MD simulation, the interaction between anacardic acid and catalytic site residues (Trp1436 and Tyr1467) are becoming weak; indicates that the molecule slightly moved away from the active site compared with the D-12 molecule. The intermolecular interaction between D-12 and Cys1438 is maintained during the entire simulation and the distances are 3.2 and 3.5 Å. This confirms that D-12 molecule is more stable than the anacardic acid in the active site of p300 HAT enzyme.