Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
Abstract
:1. Introduction
2. Results and Discussion
2.1. Validation of Docking Protocol
2.2. Molecular Docking Analysis of Prenylated Flavonoids with Glucokinase Enzyme
2.3. Molecular Dynamics Simulation
2.4. Analysis of Binding Free Energy
2.5. Molecular Modeling and Quantum Chemical Calculations
2.6. Pharmacokinetic and Drug-Likeness Studies
3. Materials and Methods
3.1. Receptor and Ligand Preparation
3.2. Validation of Docking Protocol and Molecular Docking Studies
3.3. Molecular Dynamics Simulation
3.4. Theoretical Modelling and Optimization Studies
3.5. Pharmacokinetic and Drug-Likeness Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Ligand Pubchem ID | Chemical Structure | Binding Energy (kcal/mol) | Hydrogen Bonding Interaction | Hydrophobic Interaction | Pi-Interaction | |
---|---|---|---|---|---|---|
Amino Acid Residue | Distance (Å) | |||||
Arcommunol B 101781179 | | −10.1 | Tyr61 | 2.19 | Val62, Arg63, Pro66, Ile159, Ile211, Tyr214, Val452, Val455, | Val62, Arg63, Pro66, Ile159, Ile211, Tyr214, Met235, Val452, Val455 |
Kuwanon S 6450924 | | −9.6 | - | - | Val62, Arg63, Pro66, Ile211, Tyr214, Val452, Val455, Ala456, Lys458, Lys459, | Val62, Arg63, Pro66, Ile211, Tyr214, Val452, Val455, Ala456, Lys458, Lys459. |
Manuifolin H 15837463 | | −9.5 | Leu451 | 2.05 | Val62, Arg63, Pro66, Ile211, Tyr214, Met235, Val452, Val455, | Val62, Arg63, Pro66, Ile211, Tyr214, Met235, Val452, Val455. |
Kuwanon F 156149 | | −9.4 | Val452 | 2.82 | Val62, Arg63, Pro66, Ile159, Ile211, Tyr214, Val452, Val455, | Val62, Arg63, Pro66, Ile211, Tyr214, Val452, Val455 |
Ligand | MMGBSA ΔG Bind | MMGBSA ΔG Bind Coulomb | MMGBSA ΔG Bind Covalent | MMGBSA ΔG Bind Solvation Energy | MMGBSA ΔG Bind vdW |
---|---|---|---|---|---|
Arcommunol B | −70.23 | −5.27 | 1.63 | 21.11 | −57.91 |
Kuwanon S | −54.86 | −9.12 | 2.23 | 17.20 | −50.88 |
Manuifolin H | −37.34 | −7.26 | 1.35 | 15.94 | −29.89 |
Kuwanon F | −26.76 | −8.64 | 0.97 | 14.48 | −27.12 |
Ligands | EHOMO | ELUMO | ΔE | η (Chemical Hardness) | μ (Chemical Potential) | ω (Electrophilcity Index) |
---|---|---|---|---|---|---|
Arcommunol B | −5.70 | −1.30 | 4.40 | 2.20 | −3.5 | 2.78 |
Kuwanon S | −5.83 | −1.68 | 4.15 | 2.08 | −3.76 | 3.40 |
Manuifolin H | −5.19 | −0.01 | 5.18 | 2.59 | −2.60 | 1.31 |
Kuwanon F | −5.43 | −1.31 | 4.12 | 2.06 | −3.37 | 2.76 |
Ligands | Lipinski Rule Violation | Veber Rule Violation | PAINS Test | Solubility | BBB | HIA | Acute Oral Toxicity | Carcinogenicity |
---|---|---|---|---|---|---|---|---|
Arcommunol B | 0 | 0 | 0 | −4.700 | + | + | 2.347 | - |
Kuwanon F | 0 | 0 | 0 | −4.078 | + | + | 2.612 | - |
Kuwanon S | 0 | 0 | 0 | −4.351 | + | + | 2.208 | - |
Manuifolin H | 0 | 0 | 0 | −3.392 | + | + | 1.8 | - |
PDB ID | Residues within 5 Å | Native Ligand |
---|---|---|
1V4S | Tyr61, Val62, Arg63, Ser64, Thr65, Pro66, Gln98, Ile159, Met210, Ile211, Tyr214, Tyr215, His218, Cys220, Glu221, Met235, Arg250, Leu451, Val452, Val455, Ala456 | 2-Amino−4-fluoro−5-[(1-methyl−1H-imidazol−2-yl)sulfanyl]-N-(1,3-thiazol−2-yl)benzamide |
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Faloye, K.O.; Bekono, B.D.; Fakola, E.G.; Ayoola, M.D.; Bello, O.I.; Olajubutu, O.G.; Owoseeni, O.D.; Mahmud, S.; Alqarni, M.; Al Awadh, A.A.; et al. Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach. Molecules 2021, 26, 7211. https://doi.org/10.3390/molecules26237211
Faloye KO, Bekono BD, Fakola EG, Ayoola MD, Bello OI, Olajubutu OG, Owoseeni OD, Mahmud S, Alqarni M, Al Awadh AA, et al. Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach. Molecules. 2021; 26(23):7211. https://doi.org/10.3390/molecules26237211
Chicago/Turabian StyleFaloye, Kolade Olatubosun, Boris Davy Bekono, Emmanuel Gabriel Fakola, Marcus Durojaye Ayoola, Oyenike Idayat Bello, Oluwabukunmi Grace Olajubutu, Onikepe Deborah Owoseeni, Shafi Mahmud, Mohammed Alqarni, Ahmed Abdullah Al Awadh, and et al. 2021. "Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach" Molecules 26, no. 23: 7211. https://doi.org/10.3390/molecules26237211