Theoretical investigation on known renin inhibitors and generation of ligand-based pharmacophore models for hypertension treatment

Loganathan, Lakshmanan; Sankar, Jeyanthi; Rajendran, Kannan; Muthusamy, Karthikeyan

doi:10.1080/07391102.2023.2275186

Cited by 1 publication

(1 citation statement)

References 28 publications

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“…Using the ZINC database ( www.zinc.docking.org ) 21 , the compounds were screened on ≥ 50% similarity 22 . A set of 200 compounds based on structural similarity was retrieved from the ZINC database including 1500000 compounds 23 . Molecules were converted to the pdbqt format to prepare for molecular docking study.…”

Section: Methodsmentioning

confidence: 99%

A combination of virtual screening, molecular dynamics simulation, MM/PBSA, ADMET, and DFT calculations to identify a potential DPP4 inhibitor

Zare,

Ataollahi,

Mardaneh

et al. 2024

Sci Rep

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DPP4 inhibitors can control glucose homeostasis by increasing the level of GLP-1 incretins hormone due to dipeptidase mimicking. Despite the potent effects of DPP4 inhibitors, these compounds cause unwanted toxicity attributable to their effect on other enzymes. As a result, it seems essential to find novel and DPP4 selective compounds. In this study, we introduce a potent and selective DPP4 inhibitor via structure-based virtual screening, molecular docking, molecular dynamics simulation, MM/PBSA calculations, DFT analysis, and ADMET profile. The screened compounds based on similarity with FDA-approved DPP4 inhibitors were docked towards the DPP4 enzyme. The compound with the highest docking score, ZINC000003015356, was selected. For further considerations, molecular docking studies were performed on selected ligands and FDA-approved drugs for DPP8 and DPP9 enzymes. Molecular dynamics simulation was run during 200 ns and the analysis of RMSD, RMSF, Rg, PCA, and hydrogen bonding were performed. The MD outputs showed stability of the ligand–protein complex compared to available drugs in the market. The total free binding energy obtained for the proposed DPP4 inhibitor was more negative than its co-crystal ligand (N7F). ZINC000003015356 confirmed the role of the five Lipinski rule and also, have low toxicity parameter according to properties. Finally, DFT calculations indicated that this compound is sufficiently soft.

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Section: Methodsmentioning

confidence: 99%