ABSTRACT
In order to understand the preferred modes of chelation in metal-binding peptides, quantum mechanical calculations can be used to compute energies, resulting in a hierarchy of binding affinities. These calculations often produce increasing stabilization energies the higher the coordination of the complex. However, as the coordination of a metal increases, the conformational freedom of the polypeptide chain is inevitably reduced, resulting in an entropic penalty. Estimating the magnitude of this penalty from the many different degrees of freedom of biomolecular systems is very challenging, and as a result this contribution to the free energy is often ignored. Here we explore this problem focusing on a family of phosphorylated neuropeptides that bind to aluminum. We find that there is a general negative correlation between both stabilization energy and entropy. Our results suggest that a subtle interplay between enthalpic and entropic forces will determine the population of the most favourable species. Additionally, we discuss the requirements for a possible "Metal Ion Hypothesis" based on our findings.
