In silico Drug Discovery of Two Novel Kojic Acid Metal Complex against CALM Protein for the Treatment of Alzheimer’s Disease

Abstract BACKGROUND: The current study was therefore conducted to examine the noted novel kojic acid metal complexes as potential candidates for the treatment of Alzheimer’s disease (AD) and also to study their affinity of binding with potential targets reported for AD, i.e. CALM protein. METHODS: The reported kojic acid metal complexes were created in ChemDraw 2022 software and subsequently screened based on the high-positive drug-likeness score. Using the DIGEP-Pred program, for their potential targets, Compounds having high ratings for drug-likeness were further predicted, and the interaction between changed proteins was evaluated using STRING. The Kyoto Encyclopedia of Genes and Genomes pathways database was used to record the related pathways. Ultimately, docking was completed by PyRx to determine the effectiveness of binding between the CALM protein and the kojic acid metal complexes. To see how the ligand and protein interacted, the ligand with the lowest binding energy score was selected. RESULTS: Three compounds with the highest drug-likeness scores were identified. These substances controlled several Alzheimer-related pathways. Ultimately, two compounds with the strongest anti-Alzheimer potentials were found using molecular docking and network pharmacology analysis. The docking scores of the two compounds, i.e. kojic acid complex with Zn (Comp1) and kojic acid complex with Hg (Comp 2) showed to be −7.1 kcal/mol and −7.0 kcal/mol, respectively, with CALM protein. CONCLUSION: Docking analysis showed that the kojic acid complex with Zn (Comp1) and kojic acid complex with Hg (Comp 2) had the strongest affinity for binding the CALM protein.