Insight into uranyl binding by cyclic peptides from molecular dynamics and density functional theory

Area of Science:

• Biochemistry
• Computational Chemistry
• Materials Science

Background:

• Developing effective uranyl-chelating agents is crucial for environmental remediation and nuclear waste management.
• Peptide-based chelators offer a promising avenue due to their specificity and biocompatibility.
• Computational methods are essential for understanding uranyl-peptide interactions at a molecular level.

Purpose of the Study:

• To investigate the uranyl chelation capabilities of a cyclic decapeptide and its phosphorylated derivatives.
• To explore the conformational changes induced by uranyl binding in these peptides.
• To elucidate the factors governing the stoichiometry of uranyl-peptide complexation.

Main Methods:

• Classical molecular dynamics (MD) simulations using a cationic dummy atom model for uranyl.
• Steered MD and simulated annealing to determine uranyl-peptide binding modes.
• Density functional theory (DFT) calculations for structural validation.
• Explicit water simulations to mimic physiological conditions.

Main Results:

• The cationic dummy atom model combined with MD simulations efficiently predicts uranyl-peptide binding modes.
• Uranyl binding induces significant conformational changes in the cyclic peptides, transitioning them from unstructured to organized states.
• The study explains the common 1:1 uranyl-peptide ratio due to insufficient anionic residues, except for the pS16 derivative which can bind two uranyl units.

Conclusions:

• Molecular dynamics simulations provide a cost-effective and reliable method for studying uranyl-peptide interactions.
• Phosphorylation of serine residues can enhance the uranyl-binding capacity of peptides.
• Understanding these interactions is key to designing advanced uranyl sequestration agents.