In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica
Abstract
:1. Introduction
2. Results and Discussion
2.1. Cell Viability Studies
2.2. Molecular Docking Studies
2.2.1. Redocking Analysis
2.2.2. Docking Analysis of FKB and APN on UCK2 Protein
2.3. In Vitro Kinase Activity
3. Materials and Methods
3.1. General Information
3.2. Plant Material
3.3. Extraction and Isolation of FKB and APN
3.4. Cell Culture
3.5. Drugs
3.6. Cell Viability Assay
3.7. Molecular Docking Simulation Studies
3.8. Preparation of Cell Lysate
3.9. In Vitro Kinase Activity Assay
3.10. Statistical Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ligand | Free Binding Energy * | Inhibition Constant, Ki | Intermolecular Energy * | vdW + Hbond + Desolv Energy * | Electrostatic Energy * |
---|---|---|---|---|---|
CTP | −14.27 | 34.63 pM | −16.66 | −12.59 | −4.07 |
FKB | −8.47 | 618.12 nM | −10.26 | −9.96 | −0.30 |
APN | −8.86 | 321.38 nM | −9.75 | −9.04 | −0.71 |
UCK2 | HB with CTP | HB with FKB | HB with APN |
---|---|---|---|
Active Residues | (BD ≤ 3.5 Å, DHA ≥ 90°) | (BD ≤ 3.5 Å, DHA ≥ 90°) | (BD ≤ 3.5 Å, DHA ≥ 90°) |
Thr29 | Hβ with 3′O | Oγ1 with 2 H | Hα with 3 O |
Ala30 | Hα with Oγ3, HN with Oα2 | HN with 3 O | |
Gly32 | HN with Oγ2 | ||
Lys33 | Hζ2 with Oγ2, HN with Oγ2, Hζ1 with Oα1, Hζ1 with Oβ3 | Hζ2 with 4 O | Hζ1 with 5 O |
Ser31 | HN with Oγ2 | ||
Ser34 | HN with Oγ1, Hα with Oβ1, Hβ2 with Oγ1 | Oγ with 4′ H | |
Asp62 | HN with 7 O | ||
Tyr65 | Hη with 9′ O | Hη with 10 O | |
Phe83 | |||
Asp84 | Oγ1 with 2′O, Oγ2 with 3′O | ||
Tyr112 | Oη with 4N | ||
His117 | Nδ1 with 4N | ||
Glu135 | Oε1 with 10′ H, 4′ H | Oε1 with 5 H | |
O with 10′ H | O with 7 H | ||
Arg166 | Oη12 with 3′O, Oη22 with 2′O, Oη22 with 3′O | ||
Arg169 | Hη22 with Oγ2 | Hη22 with 2 O | Hη12 with 3O |
Arg174 | Oη11 with 4′O | ||
Arg179 |
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Malami, I.; Abdul, A.B.; Abdullah, R.; Bt Kassim, N.K.; Waziri, P.; Christopher Etti, I. In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica. Molecules 2016, 21, 417. https://doi.org/10.3390/molecules21040417
Malami I, Abdul AB, Abdullah R, Bt Kassim NK, Waziri P, Christopher Etti I. In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica. Molecules. 2016; 21(4):417. https://doi.org/10.3390/molecules21040417
Chicago/Turabian StyleMalami, Ibrahim, Ahmad Bustamam Abdul, Rasedee Abdullah, Nur Kartinee Bt Kassim, Peter Waziri, and Imaobong Christopher Etti. 2016. "In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica" Molecules 21, no. 4: 417. https://doi.org/10.3390/molecules21040417