Holo-chromodulin: competition between the native Cr3+ and other biogenic cations (Fe3+, Fe2+, Mg2+, and Zn2+) for the binding sites.

Chromodulin is an oligopeptide that has an essential role for the flawless functioning of insulin. Although the precise sequence of the constituent amino acid residues and the 3D structure of the molecule has not yet been deciphered, it is known that chromodulin contains only four amino acids in the ratio of Glu-: Gly: Cys: Asp- = 4: 2: 2: 2. An indispensable part for the integrity of the molecule in its active (holo-) form are four chromium cations (hence the name) in the oxidation state of 3+, positioned in two metal binding sites containing one and three Cr3+ ions. Experimental works provide some hints/clues concerning the structure of the metal centers, although their exact composition, type, and arrangement of metal ligating entities remain enigmatic. In the current study, we endeavor to unveil possible structure(s) of the Cr3+ loaded binding sites by strictly following the evidence provided by the experimental data. Well-calibrated in silico methodology for optimization and evaluation of Gibbs free energies is applied and gives strong premises for reliably deciphering the composition/structure of chromodulin metal binding sites. Additional computations reveal the advantage of choosing Cr3+ over other tri- (Fe3+) and divalent (Fe2+, Mg2+, and Zn2+) biogenic ions for securing maximum stability of the metal-occupied binding sites.