Combining Molecular Docking and Molecular Dynamics to Predict the Binding Modes of Flavonoid Derivatives with the Neuraminidase of the 2009 H1N1 Influenza A Virus
Abstract
:1. Introduction
2. Results and Discussion
2.1. Molecular Docking and MD Simulation
2.2. Key Residues of 2009 H1N1 Neuraminidase
2.3. Flavonoid Derivatives Binding Free Energies
2.4. Free Energies Contribution Analysis of Hydrophobic and Hydrophilic Nature of 20 Flavonoids
3. Materials and Methods
3.1. Molecular Docking
3.2. Molecular Dynamics Simulation
3.3. Functionally Important Residues of H1N1 Influenza Neuraminidase
3.4. Binding Free Energies Calculations (Solvated Interaction Energies Method)
4. Conclusions
Supplementary Information
ijms-13-04496-s001.pdfAcknowledgments
- Supporting InformationThe 2D structures, experimental IC50 and experimental binding free energies of 20 flavonoid derivatives are listed in Table S1. The functional residues analysis of the 20 flavonoid derivatives are listed in Figures S1–S20. Binding free energies analysis of hydrophobic/hydrophilic nature of 20 flavonoids are listed in Tables S2–S3 and Figures S21–S23.
References
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Inhibitors | Hydrogen bonding–related residues | Non-bonding contact-related residues |
---|---|---|
1(A) | Trp179, Thr226, Asn295 | Tyr402 |
2(A) | Glu277, Asn295 | Null |
3(A) | Glu119, Asn295 | Null |
4(B) | Glu119, Ser180, Glu228, Asp294, Val346 | Null |
5(B) | Val346 | Null |
6(B) | Arg152, Glu228, Glu277 Asn295 | Null |
7(B) | Asn295 | Trp179, Ile223 |
8(B) | Glu119, Ser180, Glu228, Asp294, Val346 | Null |
9(B) | Arg152, Glu228, Val346 | Null |
10(B) | Ser180, Thr226, Glu228, Asp294 | Null |
11(B) | Glu228, Glu277 | Null |
12(B) | Asp151, Glu277, Asn325, Val346, Ser366 | Null |
13(B) | Trp179, Asn295 | Null |
14(A) | Asn295 | Null |
15(B) | Arg152, Trp179, Asn295 | Null |
16(B) | Glu119, Asp151, Ser366, Ser367, Tyr402 | Ile223, Arg368 |
17(B) | Trp179 | Null |
18(B) | Asp151, Arg152, Asn344 | Null |
19(B) | Asp151, Trp179, Glu228, Asn295 | Pro326 |
20(B) | Arg152, Trp179, Ser247, Glu277 | Null |
Inhibitors | Energy (kcal/mol) | |||||
---|---|---|---|---|---|---|
EC | Evwd | ΔMSA | ΔGbindR | ΔGbind (SIE) | ΔGbind (Experiment) | |
1 | −20.7 | −9.95 | 6.12 | −6.98 | −6.825 | −7.002 |
2 | −20.9 | −7.36 | 5.29 | −5.64 | −6.435 | −6.714 |
3 | −15.2 | −6.69 | 4.83 | −5.71 | −5.771 | −6.518 |
4 | −20.3 | −5.31 | 5.31 | −5.91 | −6.186 | −6.430 |
5 | −16.9 | −6.12 | 5.81 | −7.41 | −6.071 | −6.296 |
6 | −24.1 | −7.26 | 6.43 | −6.39 | −6.837 | −6.265 |
7 | −20.9 | −7.36 | 5.11 | −5.43 | −6.413 | −6.014 |
8 | −16.9 | −4.81 | 6.57 | −5.94 | −5.779 | −5.847 |
9 | −12.9 | −4.64 | 5.11 | −5.33 | −5.277 | −5.773 |
10 | −15.4 | −4.73 | 5.59 | −6.11 | −5.633 | −5.717 |
11 | −13.9 | −4.91 | 6.19 | −6.82 | −5.567 | −5.629 |
12 | −12.2 | −6.71 | 3.91 | −6.08 | −5.503 | −5.608 |
13 | −11.4 | −5.73 | 4.41 | −4.91 | −5.193 | −5.519 |
14 | −12.4 | −5.12 | 5.25 | −5.51 | −5.291 | −5.489 |
15 | −15.4 | −4.73 | 5.65 | −6.41 | −5.766 | −5.450 |
16 | −9.3 | −8.73 | 6.81 | −5.56 | −5.353 | −5.343 |
17 | −12.9 | −4.32 | 4.81 | −5.09 | −5.221 | −5.226 |
18 | −12.7 | −4.21 | 4.61 | −4.84 | −5.163 | −5.225 |
19 | −11.6 | −4.29 | 4.82 | −5.11 | −5.084 | −5.199 |
20 | −10.1 | −4.33 | 4.99 | −4.97 | −4.916 | −5.007 |
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Lu, S.-J.; Chong, F.-C. Combining Molecular Docking and Molecular Dynamics to Predict the Binding Modes of Flavonoid Derivatives with the Neuraminidase of the 2009 H1N1 Influenza A Virus. Int. J. Mol. Sci. 2012, 13, 4496-4507. https://doi.org/10.3390/ijms13044496
Lu S-J, Chong F-C. Combining Molecular Docking and Molecular Dynamics to Predict the Binding Modes of Flavonoid Derivatives with the Neuraminidase of the 2009 H1N1 Influenza A Virus. International Journal of Molecular Sciences. 2012; 13(4):4496-4507. https://doi.org/10.3390/ijms13044496
Chicago/Turabian StyleLu, Shih-Jen, and Fok-Ching Chong. 2012. "Combining Molecular Docking and Molecular Dynamics to Predict the Binding Modes of Flavonoid Derivatives with the Neuraminidase of the 2009 H1N1 Influenza A Virus" International Journal of Molecular Sciences 13, no. 4: 4496-4507. https://doi.org/10.3390/ijms13044496