title: Recent advances in direct phasing methods for heavy-atom substructure determination.
abstract: Macromolecular crystal structure determination has typically been a two-step process. When diffraction data from multiple chemically isomorphous or anomalously scattering crystals are available, the positions of heavy atoms from amplitude differences arising from native-derivative crystal pairs or an anomalously scattering crystal are first located and phasing of the whole protein structure is then completed using the heavy-atom substructure as a bootstrap. Shake-and-Bake, a direct-methods-based dual-space refinement procedure, provides heavy-atom substructure solutions by finding the constrained global minimum of a probabilistically defined minimal function. This minimal function relies on probabilistic estimates of the cosines of the structure invariants. A novel statistically defined minimal function that utilizes the statistical properties of the structure invariants has recently been proposed and tested. Applications of the statistical Shake-and-Bake procedure show that statistical direct methods provide a simple, reliable and efficient method of heavy-atom substructure determination.
authors.affiliation: Hauptman-Woodward Medical Research Institute and Department of Structural Biology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203, USA. xu@hwi.buffalo.edu
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xu
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Hauptman
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D019216:Metals, Heavy / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D019216:Metals, Heavy; D011506:Proteins