Metal ions and protons compete for ligand atoms in disordered peptides: Examples from computer simulations of copper binding to the prion tandem repeat

The charge and its distribution in peptides is one of the fundamental parameters in the modulation of the aggregation and folding rates. The subtle interplay between (i) the coordination chemistry of cations and their available coordination numbers, (ii) the flexibility of peptides that are intrinsically disordered, (iii) the distribution of electronegative groups within peptides, can be investigated by means of first-principle molecular dynamics simulations of peptides in contact with cations, including transition metal ions, and a sample of water solvent explicitly able to provide protons that compete with cations for the same binding sites. In this contribution recent simulations of detailed models of the prion protein tandem repeat, are reviewed, and the wealth of atomic-level information that can be extracted by this kind of simulations and by statistical methods is discussed.