Molecular flexibility and the electrostatic moments of curcumin and its derivatives in the active site of p300: A theoretical charge density study

Abstract

A molecular docking analysis and quantum chemical calculation coupled with the charge density analysis have been carried out to understand the conformational change, charge density distribution and the electrostatic properties of HAT inhibitors curcumin and its derivatives (cinnamoyl compounds) in the active site of p300. The nearest neighbours, the shortest intermolecular contacts between the inhibitors and receptor p300; their binding energies were calculated from molecular docking analysis. A high level quantum chemical calculations were performed using density functional theory (DFT-B3LYP) with the basis set 6-311G∗∗ combined with the theory of atoms in molecules (AIM) for the inhibitors in gas phase and in the active site of p300. It is observed that, when the molecules present in the active site of p300, relatively, their geometrical, bond topological and the electrostatic properties are significantly altered. The comparative study on the geometrical and electrostatic properties of these three inhibitors in gas phase and amino acid environment gives an insight on the molecular flexibility and the exact modification of electrostatic interaction of the inhibitor in the active site of p300. These fine details at electronic level allow to understand the exact drug–receptor interaction.