Journal of the American Chemical Society
A new force field for modeling metalloproteinsAuthors: Angelo Vedani and David W. Huhta
Journal: Journal of the American Chemical Society
Departments of Chemistry and Biochemistry, University of Kansas, Lawrence, Kansas, U.S.A.
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 interaction in native, complexed, and Co(II)-substituted human carbonic anhydrase I.