Abstract: | The characteristics of Ca2+-binding sites and of the structural reorganization induced by Ca2+-binding in storage proteins and ion carriers are being studied as models for molecular mechanisms in Ca2+ channels and in Ca2+-dependent modulatory proteins. A first step in the study was the development of energy parameters for Ca2+ compatible with those in the CHARMM package of computer simulation software. Such parameters were obtained from an analytical fit to the potential surface for [(Ca)(OCH2)4]2+ calculated with an ab initio molecular orbital method. The resulting parametrization was tested for the hexapeptide cyclo-(Pro-Gly)3, and a 75 residue long calcium binding protein from bovine intestine (ICaBP). The geometrical parameters calculated for the hexapeptide and its 2:1 complex with Ca2+ were in good agreement with experimental data from crystallography and nmr. Similarly, the structure of ICaBP optimized with CHARMM using the new Ca2+ parameters showed good agreement with the x-ray structure both in the local structures of the calcium-binding sites and in the overall shape of the protein. |