Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches
Abstract
:1. Introduction
2. Materials and Methods
2.1. Molecular Docking Simulation
2.2. Molecular Dynamics Simulations
2.3. Binding Free Energy Calculations
2.4. Druglikeliness and Pharmacokinetics Analyses
3. Results
3.1. Molecular Docking Simulations
3.2. Molecular Dynamics Simulation
3.3. Binding Free Energy Calculations
3.4. Druglikeliness and Pharmacokinetics Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Sl. No. | Name of the Compound | Binding Affinity (kcal/mol) | Total No. of Intermolecular Interactions | Total No. of Hydrophobic Bonds |
---|---|---|---|---|
1 | (−)-Alloaromadendrene | −6.3 | 4 | 4 |
2 | (−)-Camphene | −5.4 | 2 | 2 |
3 | (−)-Linalool | −5.7 | 11 | 10 |
4 | (+)-α-Phellandrene | −5.9 | 6 | 6 |
5 | (+)-Endo-β-bergamotene | −6.5 | 6 | 6 |
6 | (1S)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one | −5.7 | 2 | 2 |
7 | (1S, 2R, 4S)-(−)-Bornyl acetate | −6.2 | 1 | 0 |
8 | (E)-β-ocimene | −5.4 | 9 | 9 |
9 | 1S-α-pinene | −6.2 | 9 | 9 |
10 | 2,3-Dimethylaniline | −5.5 | 2 | 2 |
11 | 3-Carene | −6.1 | 6 | 6 |
12 | 4-Terpineol | −6.1 | 3 | 3 |
13 | Acetyleugenol | −6.2 | 6 | 6 |
14 | α-Fenchene | −5.8 | 7 | 7 |
15 | α-Terpineol | −5.8 | 8 | 7 |
16 | β-Caryophyllene | −6.0 | 2 | 2 |
17 | β-Pinene | −6.2 | 8 | 8 |
18 | Cis-Anethole | −5.8 | 6 | 6 |
19 | Cyclo-(L-Val-L-Leu) | −6.6 | 6 | 6 |
20 | Dehydro-p-cymene | −6.4 | 11 | 11 |
21 | Eucalyptol | −6.1 | 1 | 1 |
22 | γ-Selinene | −6.6 | 3 | 3 |
23 | Geranyl Acetate | −6.1 | 5 | 5 |
24 | Isoeugenol | −5.6 | 7 | 7 |
25 | Myrcene | −5.5 | 10 | 10 |
26 | Phytosterols | −8.3 | 3 | 2 |
Control | Saxagliptin | −7.4 | 6 | 4 |
MD Trajectory Plots | RMSD (nm) | RMSF (nm) | Rg (nm) | SASA (nm2) | Number of Ligand H-Bonds |
---|---|---|---|---|---|
Apoprotein | 0.321 | 0.262 | 2.341 | 236.25 | |
DPP4-1S-α-pinene complex | 0.287 | 0.291 | 2.349 | 237.25 | 5 |
DPP4-β-pinene complex | 0.285 | 0.245 | 2.296 | 239.60 | 5 |
DPP4-dehydro-p-cymene | 0.291 | 0.259 | 2.340 | 235.10 | 7 |
DPP4-saxagliptin complex | 0.232 | 0.250 | 2.310 | 231.12 | 4 |
Types of Binding Free Energies | DPP4-1S-α-Pinene Complex (kJ/mol) | DPP4-β-Pinene Complex (kJ/mol) | DPP4-Dehydro-p-Cymene (kJ/mol) | DPP4-Saxagliptin Complex (kJ/mol) |
---|---|---|---|---|
Van der Waal energy | −51.461 ± 10.125 | −49.871 ± 9.012 | −52.918 ± 5.670 | −39.920 ± 24.183 |
Electrostatic energy | −1.028 ± 9.716 | −0.389 ± 12.133 | −1.209 ± 6.999 | −0.214 ± 1.305 |
Polar solvation energy | 32.514 ± 12.871 | 28.574 ± 20.445 | 21.841 ± 10.001 | 22.912 ± 35.181 |
SASA energy | −3.898 ± 2.999 | −2.901 ± 2.101 | −4.996 ± 7.120 | −4.614 ± 3.652 |
Binding energy | −34.807 ± 11.099 | −27.569 ± 13.122 | −33.124 ± 14.909 | −29.752 ± 48.193 |
Categories | Types of Parameters | 1S-α-Pinene | β-Pinene | Dehydro-p-Cymene |
---|---|---|---|---|
Druglikeliness based on Lipinski’s rule of five | Molecular weight | 136.13 g/mol | 136.13 g/mol | 315.19 g/mol |
Topological polar surface area (Å) | 0.0 | 0.0 | 90.35 | |
No. of hydrogen bond donors | 0 | 0 | 3 | |
No. of hydrogen bond acceptors | 0 | 0 | 5 | |
No. of rotatable bonds | 0 | 0 | 3 | |
Adsorption | Caco-2 Permeability | −4.303 | −4.46 | −5.212 |
MDCK Permeability | 1.8e − 05 | 2e − 05 | 9.4e − 05 | |
Distribution | Volume distribution | 1.73 | 1.091 | 1.426 |
Plasma Protein Binding | 86.33% | 64.33% | 8.648% | |
Metabolism | CYP1A2 inhibition | 0.469 | 0.296 | 0.006 |
CYP2C19 inhibition | 0.267 | 0.163 | 0.029 | |
CYP2C9 inhibition | 0.312 | 0.321 | 0.039 | |
CYP2D6 inhibition | 0.012 | 0.009 | 0.019 | |
CYP3A4 inhibition | 0.034 | 0.026 | 0.338 | |
Excretion | Clearance | 15.022 | 10.097 | 8.981 |
Half-life (T 1/2) | 0.114 | 0.107 | 0.187 | |
Toxicity | Human Hepatotoxicity | 0.196 | 0.109 | 0.912 |
hERG inhibition | 0.006 | 0.005 | 0.013 | |
Carcinogenicity | 0.056 | 0.042 | 0.919 |
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Sajal, H.; Patil, S.M.; Raj, R.; Shbeer, A.M.; Ageel, M.; Ramu, R. Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches. Molecules 2022, 27, 5133. https://doi.org/10.3390/molecules27165133
Sajal H, Patil SM, Raj R, Shbeer AM, Ageel M, Ramu R. Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches. Molecules. 2022; 27(16):5133. https://doi.org/10.3390/molecules27165133
Chicago/Turabian StyleSajal, Harshit, Shashank M. Patil, Ranjith Raj, Abdullah M. Shbeer, Mohammed Ageel, and Ramith Ramu. 2022. "Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches" Molecules 27, no. 16: 5133. https://doi.org/10.3390/molecules27165133