Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation
Abstract
:1. Introduction
2. Computational Details and Methods
2.1. Molecular Dynamics (MD) Simulations
2.2. Well-Tempered Metadynamics (WT-MetaD) Simulations
3. Results and Discussion
3.1. Structural Stability of Insulin Dimer with CAGE and Ethanol
3.2. Accumulation of CAGE, Ethanol, and Water Molecules around the Insulin Dimer
3.3. Interactions of Choline, Geranate, and Ethanol with Water Molecules
3.4. Interactions between CAGE and Ethanol
3.5. Binding Free Energy (∆Gbinding) Calculations
3.6. Free Energy Landscape (FEL) of Insulin Dimer
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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System | Mole Fraction of EtOH | EtOH | Choline | Geranate | Water |
---|---|---|---|---|---|
1 | Ins-Water | 0 | 0 | 0 | 8229 |
2 | 0.10 | 30 | 270 | 270 | 3748 |
3 | 0.20 | 60 | 240 | 240 | 4111 |
4 | 0.40 | 120 | 180 | 180 | 4791 |
5 | 0.60 | 180 | 120 | 120 | 5595 |
6 | 0.80 | 240 | 60 | 60 | 6330 |
7 | 1.00 | 300 | 0 | 0 | 7183 |
System | Mole Fraction of EtOH | EtOH | Choline | Geranate | Water | REtOH | RCholine | RGeranate |
---|---|---|---|---|---|---|---|---|
1 | 0.10 | 2.79 | 27.60 | 36.27 | 256.15 | 1.35 | 1.49 | 1.96 |
2 | 0.20 | 6.93 | 25.09 | 31.56 | 279.39 | 1.71 | 1.54 | 1.93 |
3 | 0.40 | 16.83 | 21.96 | 33.34 | 274.84 | 2.44 | 2.13 | 3.23 |
4 | 0.60 | 20.20 | 11.87 | 19.64 | 218.12 | 2.88 | 2.54 | 4.20 |
5 | 0.80 | 28.13 | 6.86 | 13.84 | 237.49 | 3.12 | 3.06 | 6.19 |
6 | 1.00 | 38.66 | 00 | 00 | 297.66 | 3.11 | --- | --- |
Mole Fractions of EtOH | Enthalpy (∆H) | Entropy (∆S) | Total Binding Free Energy (∆Gbind) |
---|---|---|---|
0.10 | −49.69 | −36.94 | −12.75 |
0.20 | −50.98 | −34.88 | −16.1 |
0.40 | −49.32 | −41.08 | −8.24 |
0.60 | −47.62 | −33.88 | −13.74 |
0.80 | −50.22 | −29.72 | −20.5 |
1.00 | −50.51 | −38.50 | −12.01 |
Ins-Water | −52.20 | −34.70 | −17.5 |
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Palanisamy, K.; Prakash, M. Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation. Molecules 2022, 27, 5031. https://doi.org/10.3390/molecules27155031
Palanisamy K, Prakash M. Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation. Molecules. 2022; 27(15):5031. https://doi.org/10.3390/molecules27155031
Chicago/Turabian StylePalanisamy, Kandhan, and Muthuramalingam Prakash. 2022. "Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation" Molecules 27, no. 15: 5031. https://doi.org/10.3390/molecules27155031