RESULTS
After months of preparation and research, the molecular dynamics simulation could finally run smoothly. 4 designed peptides (TSNAVAWWLRCL, TSNAVAWTLRCL, SVWWNKY and WWTQNKY) stood out. Here are the results:
Stability of the protein
RMSD:
TSNAVAWWLRCL:
TSNAVAWTLRCL:
SVWWNKY:
WWTQNKY
Small changes (small standard deviation) of the backbone RMSD of the four-peptide showed that the length of the simulation and the structure of the peptide remained stable under simulation conditions.
Rg results:
TSNAVAWWLRCL:
TSNAVAWTLRCL:
SVWWNKY:
WWTQNKY:
The small standard deviation of the radius of gyration and the RMSD results also indicate a stable structure. We can conclude the simulation is correct and the four peptides were stable in the simulation.
Distance between the Nitrogen atom and the Pd(II):
TSNAVAWWRCL:
TSNAVAWTLRCL:
SVWWNKY:
WWTQNKY:
The minimal distacne between the Pd(II) and the nitrogen atom of trytophan residue was
| Peptide | Average(nm) | Standard deviation(nm) |
|---|---|---|
| TSNAVAWWLRCL | 1.240814273 | 0.31742214 |
| TSNAVAWTLRCL | 1.294875141 | 0.5272269 |
| SVWWNKY | 0.8264017 | 0.19382964 |
| WWTQNKY | 0.705289089 | 1.0422625 |
The Pd-N bond length in Dichlorido{2,6-diisopropyl-N-[(S)- pyrrolidin-2-ylmethyl]aniline-j2 N,N0}- palladium (II) is 2.040 Å1 and the four peptides have a distance around three to five times the length. However, since tryptophan in GROMACS is protonated, Pd (II) cannot get closer to the Nitrogen atom. The consistent distance of the tryptophan’s nitrogen and the Pd (II) indicates the four designed peptides can sequester the Pd (II) ion.
Total energy of the system:
TSNAVAWWLRCL:
TSNAVAWTLRCL:
SVWWNKY:
WWTQNKY:
Lastly, the total energy of the system was analysed. The mean and standard deviation were measured for TSNAVAWWLRCL , TSNAVAWTLRCL , SVWWNKY and WWTQNKY respectively, which were very close to our expected values from simulations of Cu2+ and Zn2+ ion binding peptides2. This proves our system fulfils the law of energy conservation. However, we must acknowledge that in silico molecular modelling cannot fully represent the experimental environment. Further in vitro analysis is required to prove the reducing ability of this part. The molecular modelling can let us gain preliminary insights on the reducing ability of the designed peptides.
| Peptide | Average (kJmol-1) | Standard deviation (kJmol-1) |
|---|---|---|
| TSNAVAWWLRCL | -178422.7609 | 617.08549 |
| TSNAVAWTRCL | -387309.6473 | 882.61857 |
| SVWWNKY | -106262.0135 | 472.53544 |
| WWTQNKY | -314810.0785 | 803.85032 |
References
[1] Nayab, S., Lee, H. I., & Jeong, J. H. (2013). Dichlorido{2,6-diisopropyl-N-[(S)-pyrrolidin-2-ylmeth-yl]aniline-κ(2) N,N'}palladium(II). Acta crystallographica. Section E, Structure reports online, 69(Pt 5), m238–m239. https://doi.org/10.1107/S1600536813008271
[2] Mahnam, K., Saffar, B., Mobini-Dehkordi, M., Fassihi, A., & Mohammadi, A. (2014). Design of a novel metal binding peptide by molecular dynamics simulation to sequester Cu and Zn ions. Research in pharmaceutical sciences, 9(1), 69–82.