title: Automating crystallographic structure solution and refinement of protein-ligand complexes.
abstract: High-throughput drug-discovery and mechanistic studies often require the determination of multiple related crystal structures that only differ in the bound ligands, point mutations in the protein sequence and minor conformational changes. If performed manually, solution and refinement requires extensive repetition of the same tasks for each structure. To accelerate this process and minimize manual effort, a pipeline encompassing all stages of ligand building and refinement, starting from integrated and scaled diffraction intensities, has been implemented in Phenix. The resulting system is able to successfully solve and refine large collections of structures in parallel without extensive user intervention prior to the final stages of model completion and validation.
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Echols
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Moriarty
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Klei
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Afonine
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge CB2 0XY, England.
authors.forename: Gábor
authors.initials: G
authors.lastname: Bunkóczi
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Headd
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge CB2 0XY, England.
authors.forename: Airlie J
authors.initials: AJ
authors.lastname: McCoy
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge CB2 0XY, England.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oeffner
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge CB2 0XY, England.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Read
authors.affiliation: Los Alamos National Laboratory, Los Alamos, NM 87545-0001, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8235, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods*; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D013917:Thrombin; D015951:Factor Xa; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1
keywords: automation; crystallographic structure solution and refinement; protein–ligand complexes