Part:BBa_K3561020

W4W5Q7

This peptide is expected to be a palladium reducing peptide. This peptide is modified by our team from the palladium reducing peptide Q7(Chiu et al., 2010). We implemented a double tryptophan structure at residues 4 and 5 as it was said that a double tryptophan is more effective than a single tryptophan structure in gold(Tan et al., 2010). We would like to investigate whether a double tryptophan will be more effective in palladium. We also want to investigate what effects will there have if we inserted the tryptophan residue at different positions.

This peptide has an isoelectric point of 6.0, a molecular weight of 0.93 kDa and hydrophobicity of 27.10. The serine residue at positions 3 and 7 are reported to be important in binding with palladium(Chiu et al., 2010). The tryptophan residue at positions 4 and 5 are reported to reduce palladium(Chiu et al., 2010). The amino acid sequence of the peptide is QQSWWIS.

References

Chiu, et al. Size-Controlled Synthesis of Pd Nanocrystals Using a Specific Multifunctional Peptide. 2010, pubmed.ncbi.nlm.nih.gov/20648291/.

DI;, Tan YN;Lee JY;Wang. Uncovering the Design Rules for Peptide Synthesis of Metal Nanoparticles. 2010, pubmed.ncbi.nlm.nih.gov/20355728/.

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Modelling

From our molecular dynamics, we were able to determine the distance of the peptide from the palladium ion, the radius of gyration, the RMSD score and the total energy of the system.

We can compare the bond lengths of our peptides with the distances reported by previous literature to evaluate the attraction between the palladium ion and the peptide. The distance should also stay consistent.

The radius of gyration represent the compactness of the peptide, the peptide is generally more stable if the standard deviation is smaller. RMSD measures the average distance each atom deviated from the start of the simulation. A small deviation in RMSD indicates a stable structure.

We have also evaluated the total energy of the system during the simulation, if the total energy of the system varies a lot, it indicates that the law of energy conservation has not been fulfilled and further in vitro analysis is required to prove its reducing ability.

More details of how our molecular dynamics is run can be found on our team wiki.

The distance of the N in indole group between threonine and Pd was evaluated for 80ns. The average and standard deviation of the distance were 0.7 nm and 1.04 nm respectively. 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 an average distance around three 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.

e root mean square deviation (RMSD) of peptide backbone atoms measures the structure of the peptide throughout the simulation. The average and standard deviation of the RMSD were 0.08 nm and 0.06 nm respectively. Radius of gyration (Rg) measures the compactness of the protein structure. The average and standard deviation of the Rg were 0.56 nm and 0.02 nm respectively. The small deviation in RMSD and Rg shows that the peptide was stable.

Total energy of the system showed conservation of energy. The average and standard deviation of the total energy were -314810 KJ/mol and 804 KJ/mol respectively. The average and standard deviation were very close to our expected values from simulations of Cu2+ and Zn2+ ion binding peptides¹. 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 binding and reducing ability of this part.

Reference

1. 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.