Insights into the role of RAHB and IHB interactions for the structure- Activity relationship of caged xanthone Morellic Acid: Spectroscopic and DFT exploration, molecular docking, and molecular dynamics simulation studies as an Antituberculosis agent

Abstract

The current study elaborates on experimental and simulated methods using density functional theory (DFT) to analyze the structure, electronic characteristics, and vibrational features of morellic acid, an isolate from Garcinia wightii. The in-depth examination of the stabilized structure indicates that the compound achieves equilibrium through conjugative, hyperconjugative, resonance-assisted hydrogen bonding (RAHB), and intramolecular hydrogen bonding (IHB) interactions, resulting in a well-supported conformation. The vibrational spectra were recorded, and the wavenumbers were comprehensively assigned using Potential Energy Distribution with a scaled quantum mechanical force field. Natural bond orbital (NBO) studies were utilized to calculate donor and acceptor bond interaction energy and electron densities. The TD-DFT computations were performed in solvent (chloroform) and gaseous phase, which agreed with the experimental values. Molecular electrostatic potential (MEP), reduced density gradient (RDG), electron localized function (ELF), and localized orbital locator (LOL) of the molecule were also analyzed. The molecular docking studies revealed that the compound holds great promise as a drug candidate for tuberculosis treatment, with the most thermodynamically stable binding score of -11.542 kcal/mol with 4BFS (protein of Mycobacterium tuberculosis PanK). The molecular dynamics (MD) simulation studies examined the stability and hydrogen bonding system of the ligand-protein complex formed between the molecule and the essential target protein for 100 ns. The findings revealed that the complex remained stable with minimal fluctuations throughout the simulation, suggesting that the molecule may prevent tuberculosis and be used as a treatment candidate.