2022
DOI: 10.1371/journal.pone.0266632
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Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations

Abstract: Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation. Elevated IL-6 levels have been identified in several severe disorders such as sepsis, acute respiratory distress syndrome (ARDS), and most recently, COVID-19. The biological activity of IL-6 relies on interactions with its specific receptor, IL-6Rα, including the membrane-bound IL-6 receptor (mIL-6R) and the soluble IL-6 receptor (sIL-6R). Thus, inhibition of the interaction between these… Show more

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Cited by 31 publications
(12 citation statements)
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“…The hydrogen bond interactions between protein and ligand across the entire MD simulations are crucial for the stability of a protein–ligand complex. Here, hydrogen bond analysis between protein and ligand was performed by using the “Hydrogen bond” plugin in VMD with a distance and angle cutoff of 3.5 Å and 120°, respectively. , In the present study, we considered the hydrogen bond occupancy to be greater than 20% for a significant contribution to protein–ligand interactions. All ligands acted as hydrogen bond donors and also as acceptors.…”
Section: Resultsmentioning
confidence: 99%
“…The hydrogen bond interactions between protein and ligand across the entire MD simulations are crucial for the stability of a protein–ligand complex. Here, hydrogen bond analysis between protein and ligand was performed by using the “Hydrogen bond” plugin in VMD with a distance and angle cutoff of 3.5 Å and 120°, respectively. , In the present study, we considered the hydrogen bond occupancy to be greater than 20% for a significant contribution to protein–ligand interactions. All ligands acted as hydrogen bond donors and also as acceptors.…”
Section: Resultsmentioning
confidence: 99%
“…During the simulations, the hydrogen bonds could form between the small-molecule ligands and the MPXV E8 protein residues. In this study, the hydrogen bonds were defined to occur if the bonding angle between the hydrogen donor (D) and acceptor (A) D-H⋯A larger than 120° with the distance between D and A not exceeding 3.5 Å [ 45 ]. The GROMACS prebuilt commands were used to calculate the root mean square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA) of the protein backbone or the heavy atoms of the ligands for further evaluation.…”
Section: Methodsmentioning
confidence: 99%
“…In a study conducted by Tran Que-Huong et al, a pharmacophoric inhibitor was generated against IL-6Rα, called ZINC83804241. [7] The compound (ZINC83804241) was downloaded from the ZINC database and docked onto IL-6Rα using Autodock Vina to compare the affinity expressed by the inhibitor molecule suggested in this study and ZINC83804241.…”
Section: Final Molecular Docking Runmentioning
confidence: 99%
“…In the study conducted by Tran Que-Huong et al, a pharmacophoric inhibitor was generated against IL-6Rα. [7] Their inhibitor of choice (ZINC83804241) was docked onto IL-6Rα using Autodock Vina. This inhibitor expressed a binding affinity of À 5.9 kcal/mol.…”
Section: Comparative Analysis Between the Top Compound (L821) And Zin...mentioning
confidence: 99%
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