Molecular dynamics simulations on constraint metal binding peptides

Molecular dynamics (MD) simulations are performed using constraint polypeptides that were combinatorially selected to have binding affinities for the noble metal platinum (Pt). We analyzed the effects of the threonine-serine-threonine (T-S-T) amino acid sequence because this domain is common among strong binders. Using pair correlation functions, intermolecular interactions are evaluated between peptide residues and the metal surface in the presence of solvent water. In explicit simulations in the absence of metal surface, we find that among the experimentally verified strong binders the side chain groups within the T-S-T region make hydrogen bonding with water molecules, i.e. being more solvent exposed. In MD simulations including the metal, the T-S-T region interacts with the substrate to an extent greater than those with the non-polar residues. However, it is also observed that carbonyl and amide groups on the backbone and certain residues, such as Arg and Pro, also exhibit close interactions with the surface. Backbone torsional angle auto-correlation functions indicate that threonine and serine residues impart the highest flexibility to the backbone of the chains in solvent simulations in the absence of the surface. This flexibility of the peptides and their interactions with the metal surface are major players in binding. The simulations also reveal that the flexibility of the whole chain is considerably hindered upon binding. These results have significant implications in understanding of how constraint peptides selectively bind to a metal surface and may provide insight into the design of new sequences.