Zinc metalloenzymes carry out essential functions in a wide variety of biochemical pathways and have attracted much attention as drug design targets; examples include the anthrax toxin lethal factor (LF) and the matrix metalloproteinases (MMP's). However, reliable in silico representation of zinc centers in macromolecules is nontrivial due to the complexity of the coordination environment and charge distribution at the catalytic center. The EE-MB method has emerged as a particularly promising approach in enabling accurate simulations on biozinc systems. In the present work, we recommend a set of specific fragmentation strategies to enhance the accuracy of EE-MB for neutral and negatively charged penta- and hexacoordinate Zn systems. We find that the electrostatically embedded three-body (EE-3B) method reproduces conventionally obtained bond dissociation energies in a series of penta- and hexacoordinate zinc systems with an average absolute error (averaged over 25 cases) of only 0.98 kcal/mol.

Application of the electrostatically embedded many-body (EE-MB) approximation method to penta- and hexacoordinate zinc model systems

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.