title: QM/MM X-ray refinement of zinc metalloenzymes.
abstract: 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 R(free) 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.
authors.affiliation: Department of Chemistry and the Quantum Theory Project, 2328 New Physics Building, PO Box 118435, University of Florida, Gainesville, FL 32611-8435, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Seth A
authors.initials: SA
authors.lastname: Hayik
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Merz
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D045727:Metalloexopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
chemical_list: D005656:Fungal Proteins; D000426:Alcohol Dehydrogenase; D045727:Metalloexopeptidases; D015032:Zinc