QM/MM X-ray refinement of zinc metalloenzymes

Zinc metalloenzymes play an important role in biology. However, due to the limitation of molecular force field energy restraints used in X-ray refinement at medium or low resolutions, the precise geometry of the zinc coordination environment can be difficult to distinguish from ambiguous electron density maps. Due to the difficulties involved in defining accurate force fields for metal ions, the QM/MM (quantum-mechanical/molecular-mechanical) method provides an attractive and more general alternative for the study and refinement of metalloprotein active sites. Herein we present three examples that indicate that QM/MM based refinement yields a superior description of the crystal structure based on R and Rfree values and on the inspection of the zinc coordination environment. It is concluded that QM/MM refinement is an useful general tool for the improvement of the metal coordination sphere in metalloenzyme active sites.

Graphical abstractThe comparison of three coordination environments of Zn2+ ions between the deposited PDB structures (green) and QM/MM re-refined structures (gray).Figure optionsDownload full-size imageDownload as PowerPoint slide