Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protein Preparation
2.2. Docking and Molecular Dynamics (MD) Simulations
2.3. Free Energy Perturbation (FEP) Calculations
3. Results
3.1. Selection of the AT2R Agonists Dataset and Initial Docking
3.2. Molecular Dynamics Simulations of Octapeptides and Mimetics (Compounds 1–6)
3.3. Selectivity between AT1R and AT2R
3.4. FEP Simulations of the Pentapeptides and Mimetics 7–11
3.5. Putative Binding Mode of C21
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ligand Pair | Chemical Modification | ΔΔGexp ± SEM (kcal/mol) | ΔΔGcalc ± SEM (kcal/mol) |
---|---|---|---|
8 → 7 | Ile → Phe | 1.54 ± 0.06 | 0.97 ± 0.64 |
10 → 9 | Ile → Phe | 2.38 ± 0.07 | 0.55 ± 0.67 |
11 → 9 | Aniline → Phenyl | 0.59 ± 0.06 | 0.46 ± 0.36 |
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Vasile, S.; Hallberg, A.; Sallander, J.; Hallberg, M.; Åqvist, J.; Gutiérrez-de-Terán, H. Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists. Biomolecules 2020, 10, 649. https://doi.org/10.3390/biom10040649
Vasile S, Hallberg A, Sallander J, Hallberg M, Åqvist J, Gutiérrez-de-Terán H. Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists. Biomolecules. 2020; 10(4):649. https://doi.org/10.3390/biom10040649
Chicago/Turabian StyleVasile, Silvana, Anders Hallberg, Jessica Sallander, Mathias Hallberg, Johan Åqvist, and Hugo Gutiérrez-de-Terán. 2020. "Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists" Biomolecules 10, no. 4: 649. https://doi.org/10.3390/biom10040649