Molecular Docking Study for Prediction of Chiral HPLC Separation of Hydroxychloroquine as an Alternative Antiviral of SARS-CoV-2

Abstract:

The HPLC chiral separation of hydroxychloroquine (HCQ) using chiral α-1-acid glycoprotein (AGP) column has been predicted based on a molecular docking approach. The research begins with the geometrical optimization of the HCQ compound using the quantum calculation method of semiempirical (SE) of PM6, AM1, and PM3, and Hartree-Fock (HF) and density functional theory (DFT/B3LYP) with the basis set of 3-21G, 6-31G, and 6-311G. Molecular docking was performed with AutoDock Vina and PyRx applications on exhaustiveness of 264. Redocking with AutoDock Vina was done using coordinates of X = 13.584; Y = 1.47; Z = 18.451 with a grid box size of 40 x 40 x 40 and a grid Spacing of 0.375 Å, followed by specific docking process using the same conditions as redocking. The DFT method with the basis set of 6-311G was the best calculation method because it gives the lowest PRESS and closest r² value to one for the comparison between calculated and experimental data of ¹H-NMR. The docking result shows that R-HCQ enantiomer has more negative value of binding energy and more diverse interactions in the inclusion complex, indicating that R-HCQ forms more stable complex with AGP, and therefore it will be retained longer in the AGP column and eluted from the column later after R-HCQ.

• Periodical: Advances in Science and Technology (Volume 115)
• Pages: 15-22
• DOI: https://doi.org/10.4028/p-r9unm9
• Online since: August 2022
• Authors: Prisca Caesa Moneteringtyas*, Agus Kuncaka, Dadan Hermawan, Mudasir Mudasir
• Keywords: Docking Molecular, Hydroxychloroquine, α1-Acid Glycoprotein

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