Computational and experimental design of L-amino acid-based alternatives to ketorolac
Abstract
L-amino acids play a vital role in various biological processes, including hormone production, adipose tissue growth and repair, and protein synthesis. Consequently, the design of novel L-amino acid-based drugs with fewer side effects has recently garnered significant attention. Ketorolac, while effective for pain reduction, presents several adverse side effects, motivating the search for alternatives. An ideal alternative should structurally resemble ketorolac but offer improved chemical and thermal stability, as well as enhanced hydrogen bonding capability. In this project, we designed an L-amino acid-based structure as a potential alternative to ketorolac. Using computer-aided drug discovery methods, we generated a detailed, atomic-level description of the drug ligand and evaluated its selectivity properties, ADMET prediction, and Pre-Tox analysis. Molecular docking calculations were then performed to identify the most favorable active site for the newly designed ligand, mimicking ketorolac's binding pose within the protein. The resulting AVH structure exhibited a close resemblance to ketorolac. After these initial assessments, we performed molecular dynamics simulations. The RMSD and RMSF plots indicate the stability of the dynamic structure of the substituted ligand. Analysis of the rotation and hydrogen bond plots revealed strong interactions between the protein and the ligand. Furthermore, analysis of the protein secondary structure and residue-wise secondary…
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