Probing the effect of intermolecular interaction and understanding the electrostatic moments of anacardic acid in the active site of p300 enzyme via DFT and charge density analysis

A charge density analysis has been performed on gas phase and docked forms of anacardic acid molecule to understand its charge density distribution, electrostatic moments and the conformation in the active site of p300 enzyme. Here, we report the binding affinity of anacardic acid with the p300 enzyme calculated from docking analysis. The charge density distribution of anacardic acid molecule in the gas phase as well as the docked form has been determined from the high level quantum chemical calculations using HF and DFT methods coupled with AIM theory. The charge density study on both forms of anacardic acid differentiates its structural and the electrostatic properties in different environments. When the molecule enters into the active site of p300 its conformation, charge density distribution, dipole moment and electrostatic potential are significantly altered in comparison to its gas phase structure. In the active site, the molecule adopts different conformations, its pentadecyl chain is found to be highly twisted; the charges are redistributed and the dipole moment increases from 2.37 to 3.17 D. Due to the charge redistribution, the electronegative region of carboxyl group increased as it is found small in the gas phase. The comparisons between both forms reveal the flexibility of anacardic acid in the active site.

The charge density study on gas phase and the docked forms of anacardic acid (AA) shows the difference of conformational, bond topological and the electrostatic properties. When the molecule (gas phase) enters into the active site of p300, it gets folded and the dipole moment increases from 2.37 to 3.17 D. The electrostatic potential of the molecule also altered, specifically, the electronegative region of carboxyl group increases as it is small in the gas phase.Figure optionsDownload high-quality image (167 K)Download as PowerPoint slideHighlights
► The conformational geometry of anacardic acid from docked form is different from its gas phase geometry.
► The pentadecyl chain of the molecule significantly twisted in the active site of p300 enzyme.
► A high charge density redistribution and large increase in molecular dipole moment observed when anacardic acid present in the active site.
► A large electronegative ESP region is found at the vicinity of oxygen atoms.
► Several strong intermolecular hydrogen bonding interactions are noticed between anacardic acid–p300, which alters the structure and electrostatic properties of anacardic acid.