Molecular Docking Approach for Prediction of Chromatographic Chiral Separation of Ketorolac Using AGP Column

Abstract

Prediction of chiral separation of R- and S-ketorolac has been carried out using a molecular docking approach. Geometry optimization using different calculation methods suggests that Hartree-Fock (HF)/6-31G is the best method to describe the most stable ketorolac structure. Docking studies have been performed on AutoDock and Gaussian software. Molecular docking results were used to predict the separation of ketorolac enantiomers in the AGP (alpha-1-acid-glycoprotein) chiral column by comparing the binding energies and types of interaction. To ensure the accuracy of the results, not only specific docking was performed, but blind docking was also conducted in this study. The results of the study show that the binding energy of S-ketorolac is more negative than that of R-ketorolac, indicating that stronger interaction between S-ketorolac and AGP occurs. Therefore, the R-ketorolac will be eluted first from the AGP column followed by S-ketorolac. As expected, this prediction is in good agreement with the experimental results of the separation of ketorolac enantiomers.