The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study

Abstract

The decreasing rate of metabolisms within the mitochondrial is connected to the progressive characterization of Alzheimer's Disease (AD). Dihydrolipoamide dehydrogenase (dld), and DLD1 are specific chemicals comprised of two enzymes/complexes of protein; pyruvate dehydrogenase and α-ketoglutarate dehydrogenase physiologically related to AD and have a noteworthy function in energy metabolism. The present computational study was designed to envisage a rational screening of natural phytochemical compounds against DLD1 in AD. The molecular docking and virtual screening approaches were adopted within the best binding active sites of DLD1 in AD to screen 15,282 medicinal phytochemicals’ libraries, which were developed from the literature search, PubChem, Zinc Database, and MPD3 Database. This docking followed by MD-simulation of the best three complexes (1-Caffeoyl-4-deoxyquinic acid, N-Butyryl Coenzyme A, Precatorine) determined through docking scores, RMSD-refine, Pharmacokinetics properties, pharmacological analysis, molinspiration, ADMET-properties, and binding energies. The top complexes with docking-S scores (-13.7117, -12.4565, -11.6440), RMSD-refine values (1.64, 0.86, 0.93), and interactive hits/residues (Arg216, Leu263, Ile125, Met262, Asp256), showed a binding affinity with another catalytic active site domain-chain A (residues 86-293). Although this in-silico work is not experimentally determined, the affinity and interactions of these selected novel compounds might help to design the therapeutics against Alzheimer’s Disease.

Keywords

• Alzheimer’s disease, Dihydrolipoamide dehydrogenase (DLD1), Molecular docking, Natural medicinal compounds, MD-simulation, Pharmacokinetics analysis.