Exploring the molecular structure, vibrational spectroscopic, quantum chemical calculation and molecular docking studies of curcumin: A potential PI3K/AKT uptake inhibitor

Abstract

The IUPAC name of curcumin is (1E, 6E)-1,7-Bis(4-hydroxy-3methoxyphenyl) hepta-1,6-e-3,5-dione (7B3M5D) and is characterized by spectroscopic profiling with FT-IR and FT-Raman spectra obtained both experimentally and theoretically. PED analysis was done for the confirmation of minimum energy obtained in the title compound. Optimized geometrical parameters are compared with experimental values obtained for 7B3M5D by utilizing B3LYP functional employing 6-311++G (d,p) level of theory. The HOMO-LUMO, MEP, and Fukui function analysis has been used to elucidate the information regarding charge transfer within the molecule. The stabilization energy and charge delocalization of the 7B3M5D were performed by NBO analysis. This article assesses that the title compound act as a potential inhibitor of the PI3K/AKT inhibitor through in silico studies, like molecular docking, molecular dynamics (MD), ADMET prediction and also this molecule obeys Lipinski's rule of five. 7B3M5D was docked effectively in the active site of PI3K/AKT inhibitor.

Keywords: ADMET prediction; Docking; FT-IR; FT-Raman; Molecular dynamics and molecular.

Figure 1

Optimized geometrical structure with atomic labeling of 7B3M5D.

Figure 2

a) FT-IR and b) FT-Raman spectra of 7B3M5D (Experimental & Theoretical).

Figure 3

The atomic orbital composition of the frontier molecular orbital 7B3M5D.

Figure 4

Mulliken atomic charge distribution of 7B3M5D molecule.

Figure 5

Molecular electrostatic potential (MEP) for the 7B3M5D molecule.

Figure 6

Cartoon representations of the ligand-protein complex and binding mode of interacting amino acid residues of 7B3M5D-PI3K/AKT inhibitor complex.

Figure 7

Ligplot view of hydrophobic and hydrogen bonding interaction in the active site of PI3K/AKT inhibitor.

Figure 8

Surface view of encapsulated in the binding cavity of the 7B3M5D in the PI3/AKT inhibitor.

Figure 9

a) Root Mean Square Deviation (RMSD) plot of the backbone atom for PI3K/AKT inhibitor- 7B3M5D complex (b) the RMSF of the amino acid residues of target PI3K/AKT-7B3M5D complex during MD simulation.

Figure 10

a) Hydrogen bonding interaction of complex b) The Interaction Energy of PI3K/AKT inhibitor- 7B3M5D complex. The total (green), Van der Waals (blue) and Electrostatic (pink) interaction energy between PI3K/AKT in MD simulation.