Identification of Terpenoids From Abrus precatorius Against Parkinson’s Disease Proteins Using In Silico Approach

Abstract

Parkinson’s disease (PD) is the second major neuro-degenrative disorder that causes morbidity and mortality among older populations. Terpenoids were reported as potential neuro-protective agents. Therefore, this study seeks to unlock the inhibitory potential of terpenoids from Abrus precatorius seeds against proteins involve in PD pathogenesis. In this study, in silico molecular docking of 5 terpenoids derived from high-performance liquid chromatography (HPLC) analysis of A. precatorius seeds against α-synuclein, catechol-o-methyltransferase, and monoamine oxidase B which are markers of PD was performed using Autodock vina. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) of the hits were done using Swiss ADME predictor and molecular dynamic (MD) simulation of the hit-protein complex was performed using Desmond Schrodinger software. Five out of 6 compounds satisfied the ADME/Tox parameters and showed varying degrees of binding affinities with selected proteins. Drimenin-α-synuclein complex showed the lowest binding energy of −9.1 kcal/mol followed by interaction with key amino acid residues necessary for α-synuclein inhibition. The selection of this complex was justified by its stability in MD simulation conducted for 10 ns and exhibited stable interaction in terms of root mean square deviation (RMSD) and root mean square deviation error fluctuation (RMSF) values.

HPLC/ESI‐MS Characterization of Phenolic Compounds from Cnicus benedictus L. Roots: A Study of Antioxidant, Antibacterial, Anti‐Inflammatory, and Anti‐Alzheimer's Activity

“…The polyphenols and standard compound (quercetin) were docked against the active site of the target using the binding site of the co‐crystalized ligand, which was removed during protein preparation. Grid coordinate 27.59, 18.35, 25.00 for x, y, z respectively of the binding pocket of 3V99 was employed with the binding energies estimated by auto dock vina from PyRx [59] . Visualization of the molecular interaction of the polyphenols and amino acid residues of the binding site was carried out using discovery studio 2020.…”

“…Grid coordinate 27.59, 18.35, 25.00 for x, y, z respectively of the binding pocket of 3V99 was employed with the binding energies estimated by auto dock vina from PyRx. [59] Visualization of the molecular interaction of the polyphenols and amino acid residues of the binding site was carried out using discovery studio 2020.…”

The inhibitory effect of common food spices bioactive compounds against KRAS G12C and KRAS G12D: an in-silico approach

“…NPT ensemble was used to run the simulation for 150 ns. To measure the stability of the complexes in their natural motion, the root mean square deviation (RMSD), root mean square uctuation (RMSF), intermolecular interaction, and ligand torsion pro le were calculated (Omoboyowa et al, 2021).…”

“…For small globular proteins, changes of the order of 1-3 A o are quite acceptable. However, changes much larger than that of the protein suggest the protein is going through a signi cant structural shift throughout the simulation (Omoboyowa et al, 2021). The ligand has probably diffused away from its initial binding site if the reported ligand RMSD value is much greater than the RMSD of the protein (Allegra et al, 2021).…”

“…Successful drugs have strong pharmacokinetic properties and maintain the rules of ve for potential drug candidates as postulated by Lipinski, which is commonly known as Lipinski's rules of ve (More-Adate et al, 2022). In recent times, computational techniques have been deployed to speed up and reduce the cost associated with the process of determining the ADMET properties of a drug(Omoboyowa et al, 2021). Most drugs are administered orally and must pass through the gastrointestinal barrier before being absorbed by the body(Yan et al, 2008).…”