title: Polarizable atomic multipole x-ray refinement: hydration geometry and application to macromolecules.
abstract: We recently developed a polarizable atomic multipole refinement method assisted by the AMOEBA force field for macromolecular crystallography. Compared to standard refinement procedures, the method uses a more rigorous treatment of x-ray scattering and electrostatics that can significantly improve the resultant information contained in an atomic model. We applied this method to high-resolution lysozyme and trypsin data sets, and validated its utility for precisely describing biomolecular electron density, as indicated by a 0.4-0.6% decrease in the R- and R(free)-values, and a corresponding decrease in the relative energy of 0.4-0.8 Kcal/mol/residue. The re-refinements illustrate the ability of force-field electrostatics to orient water networks and catalytically relevant hydrogens, which can be used to make predictions regarding active site function, activity, and protein-ligand interaction energies. Re-refinement of a DNA crystal structure generates the zigzag spine pattern of hydrogen bonding in the minor groove without manual intervention. The polarizable atomic multipole electrostatics model implemented in the AMOEBA force field is applicable and informative for crystal structures solved at any resolution.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, California, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Fenn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schnieders
authors.forename: Axel T
authors.initials: AT
authors.lastname: Brunger
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D015203:Reproducibility of Results; D055672:Static Electricity; D013379:Substrate Specificity; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry*
chemical_list: D046911:Macromolecular Substances; D014867:Water; D004247:DNA; D009113:Muramidase; D014357:Trypsin