An empirical potential function for metal centers: Application to molecular mechanics calculations on metalloproteins

At present, most molecular mechanics programs that model metalloproteins do not allow for specific geometric requirements at metal centers. An analysis of small‐molecule crystal structures containing four‐, five‐, and six‐coordinated zinc, retrieved from the Cambridge Structural Database (CSD), leads to a new metal‐center potential function for use in molecular mechanisc programs. This potential function includes as variables the metal‐ligand separations and the angles subtended at the metal and allows specifically for distortions from frequently occurring types of coordination geometries (e.g. tetrahedron square pyramid, trigonal bipyramid, and octahedron). The combination of such a metal‐center potential function and one for hydrogen bonds allowing for Ione‐pair directionality makes monopole electrostatic contributions to the force‐field energy superfluous, thus circumventing many problems associated with the assignment to the force‐field energy superfluous, thus circumventing many problems associated with the assignment of atomic apartial charges and a dielectric constant. The molecular mechanics program ‘YETI’, containing both types of potential functions, has been used to refine details of substrate binding of 16 complexes of human carbonic anhydrase II with small molecules. The stereochemistry of the refined complexes is in good agreement with data retrived from the CSD and hence allows realistic structure activity relationships.