Difference between revisions of "Part:BBa K3561002"

Revision as of 15:26, 26 October 2020

A6C11(Coppage et al., 2013)

A6C11 is a palladium binding peptide. It is used as a library peptide in our project to act as a template for our mutations. The results of molecular dynamics for our modified peptides are also compared with this peptide. This peptide has an isoelectric point of 9.0, a molecular weight of 1.25kDa and hydrophobicity of 24.06. The alanine residue at position 6 has a minimal binding with palladium while the cysteine residue at position 11 has a strong binding with palladium, it was suggested that this may have higher efficiency(Coppage et al., 2013). The arginine residue at position 10 is reported to coordinate with palladium(Pacardo et al., 2009). The serine and threonine residues at positions 1 and 2 are also reported to be important in binding with palladium(Sarikaya et al., 2003). The amino acid sequence TSNAVAPTLRCL.

References

Pacardo, et al. “Biomimetic Synthesis of Pd Nanocatalysts for the Stille Coupling Reaction.” ACS Nano, U.S. National Library of Medicine, 2009, pubmed.ncbi.nlm.nih.gov/19422199/.

Sarikaya et al. “Molecular Biomimetics: Nanotechnology through Biology.” Nature News, Nature Publishing Group, 2003, www.nature.com/articles/nmat964.

Coppage, et al. “Exploiting Localized Surface Binding Effects to Enhance the Catalytic Reactivity of Peptide-Capped Nanoparticles.” Journal of the American Chemical Society, U.S. National Library of Medicine, 2013, pubmed.ncbi.nlm.nih.gov/23865951/.

Sequence and Features

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 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 0.285 nm and 0.0552 nm respectively. Radius of gyration (Rg) measures the compactness of the protein structure. The average and standard deviation of the Rg were 0.691 nm and 0.0515 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 -264000 KJ/mol and 738 KJ/mol respectively. The average and standard deviation 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 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.