title: A flexible and efficient procedure for the solution and phase refinement of protein structures.
abstract: An ab initio method is described for solving protein structures for which atomic resolution (better than 1.2 A) data are available. The problem is divided into two stages. Firstly, a substructure composed of a small percentage ( approximately 5%) of the scattering matter of the unit cell is positioned. This is used to generate a starting set of phases that are slightly better than random. Secondly, the full structure is developed from this phase set. The substructure can be a constellation of atoms that scatter anomalously, such as metal or S atoms. Alternatively, a structural fragment such as an idealized alpha-helix or a motif from some distantly related protein can be orientated and sometimes positioned by an extensive molecular-replacement search, checking the correlation coefficient between observed and calculated structure factors for the highest normalized structure-factor amplitudes |E|. The top solutions are further ranked on the correlation coefficient for all E values. The phases generated from such fragments are improved using Patterson superposition maps and Sayre-equation refinement carried out with fast Fourier transforms. Phase refinement is completed using a novel density-modification process referred to as dynamic density modification (DDM). The method is illustrated by the solution of a number of known proteins. It has proved fast and very effective, able in these tests to solve proteins of up to 5000 atoms. The resulting electron-density maps show the major part of the structures at atomic resolution and can readily be interpreted by automated procedures.
authors.affiliation: Physics Department, University of York, York YO10 5DD, England.
authors.forename: J
authors.initials: J
authors.lastname: Foadi
authors.forename: M M
authors.initials: MM
authors.lastname: Woolfson
authors.forename: E J
authors.initials: EJ
authors.lastname: Dodson
authors.forename: K S
authors.initials: KS
authors.lastname: Wilson
authors.forename: Y
authors.initials: Y
authors.lastname: Jia-xing
authors.forename: Z
authors.initials: Z
authors.lastname: Chao-de
mesh_terms: D000465:Algorithms; D018360:Crystallography, X-Ray / Q000379:methods; D005583:Fourier Analysis; D008432:Mathematical Computing; D008956:Models, Chemical; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D010446:Peptide Fragments; D011506:Proteins