A NEW FORCE-FIELD FOR MODELING METALLOPROTEINS

We present the development of a force field for the simulation of metalloproteins featuring a new potential function for modeling metal-ligand interactions. This function includes as variables the metal-ligand separations, the symmetry at the metal center, directionality of the metal-ligand bonds, ligand-metal charge transfer, and (for transition-metal ions) ligand-field stabilization. The function was developed based on the analysis of accurate small-molecule crystal structures retrieved from the Cambridge Structural Database and incorporated into the molecular mechanics program “yeti” which also includes directional terms for H-bonds and salt linkages in its force field energy expression. The program was then used to model details of metal-coordination, H-bond network formation and protein-solvent interactions in native, complexed, and Co(II)-substituted human carbonic anhydrase I. © 1990, American Chemical Society. All rights reserved.