Despite its numerous biological applications it is difficult

Despite its numerous biological applications, it is difficult to confirm the binding of Zn to proteins or deduce its coordination geometry. Why?

Solution

Metal ions are essential to maintain the function, structure, and stability of proteins and, as the second abundant metal ion found in eukaryotic organisms, zinc plays important roles in many biological processes.

In conventional protein structure prediction methods, interactions among protein atoms are often approximated using pair-additive distance-dependent potentials. This approach is problematic for modeling metal–protein interactions because formation of correct metal coordination geometries requires simultaneous satisfaction of distance, angle, and dihedral geometric constraints from multiple protein atoms surrounding the ion.

It has been well established that the majority of the structural zinc-binding sites are arranged in a tetrahedral coordination, and the most preferred zinc-liganding residues in these sites are cysteines and histidines. To capture this coordination geometry, zinc is represented as a ligand with five atoms forming the center and vertices of a tetrahedron. The actual zinc atom is centered in the tetrahedron and each of the four virtual atoms occupies a vertex. The distance between zinc and a virtual atom, 2.20 Å . The four virtual atoms defined in the zinc residue serve to

(1) set a reference frame for calculating the internal rigid-body transformation from the protein to the zinc, and

(2) define constraints consistent with the coordination geometry between the zinc and the coordinating residues.