PHENIX: a comprehensive Python-based system for macromolecular structure solution

doi:10.1107/S0907444909052925

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PHENIX: a comprehensive Python-based system for macromolecular structure solution

Journal Article•DOI•

PHENIX: a comprehensive Python-based system for macromolecular structure solution

Paul D. Adams¹, Paul D. Adams², Pavel V. Afonine², Gábor Bunkóczi³, Vincent B. Chen⁴, Ian W. Davis⁴, Nathaniel Echols², Jeffrey J. Headd⁴, Li-Wei Hung⁵, Gary J. Kapral⁴, Ralf W. Grosse-Kunstleve², Airlie J. McCoy³, Nigel W. Moriarty², Robert D. Oeffner³, Randy J. Read³, David S. Richardson⁴, Jane S. Richardson⁴, Thomas C. Terwilliger⁵, Peter H. Zwart² - Show less +15 more•Institutions (5)

University of California, Berkeley¹, Lawrence Berkeley National Laboratory², University of Cambridge³, Duke University⁴, Los Alamos National Laboratory⁵

01 Feb 2010-Acta Crystallographica Section D-biological Crystallography (International Union of Crystallography)-Vol. 66, Iss: 2, pp 213-221

TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.

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Abstract: Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.

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Journal Article•DOI•

J. Appl. Cryst.の発刊に際して

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良二上田

10 Mar 1970

8,159 citations

Journal Article•DOI•

Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix

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Dorothee Liebschner¹, Pavel V. Afonine¹, Matthew L. Baker², Gábor Bunkóczi³, Vincent B. Chen⁴, Tristan I. Croll³, Bradley J. Hintze⁴, Li-Wei Hung⁵, Swati Jain⁴, Airlie J. McCoy³, Nigel W. Moriarty¹, Robert D. Oeffner³, Billy K. Poon¹, Michael G. Prisant⁴, Randy J. Read³, Jane S. Richardson⁴, David S. Richardson⁴, Sammito³, Oleg V. Sobolev¹, Duncan H. Stockwell³, Thomas C. Terwilliger⁵, Alexandre Urzhumtsev⁶, Alexandre Urzhumtsev⁷, Lizbeth L. Videau⁴, Carmen J. Williams⁴, Paul D. Adams⁸, Paul D. Adams¹ - Show less +23 more•Institutions (8)

Lawrence Berkeley National Laboratory¹, Baylor College of Medicine², University of Cambridge³, Duke University⁴, Los Alamos National Laboratory⁵, University of Lorraine⁶, French Institute of Health and Medical Research⁷, University of California, Berkeley⁸

01 Oct 2019

TL;DR: Recent developments in the Phenix software package are described in the context of macromolecular structure determination using X-rays, neutrons and electrons.

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Abstract: Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks.

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3,268 citations

Cites background or methods from "PHENIX: a comprehensive Python-base..."

...RNA ribose pucker outliers are diagnosed by a simple relationship between the well fit 30 phosphate and glycosidic bond direction (Richardson et al., 2008), which also enables puckerspecific geometry targets in refinement (Adams et al., 2010)....
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...Phenix Phenix (Adams et al., 2002, 2010) is a software suite that uses reduced data from X-ray diffraction, electron diffraction, neutron diffraction or cryo-EM to determine macromolecular structures....
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Journal Article•DOI•

MolProbity: More and better reference data for improved all-atom structure validation.

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Christopher J. Williams¹, Jeffrey J. Headd¹, Nigel W. Moriarty², Michael G. Prisant¹, Lizbeth L. Videau¹, Lindsay N. Deis¹, Vishal Verma³, Daniel A. Keedy¹, Bradley J. Hintze¹, Vincent B. Chen¹, Swati Jain¹, Steven M. Lewis¹, W. Bryan Arendall¹, Jack Snoeyink³, Paul D. Adams², Simon C. Lovell⁴, Jane S. Richardson¹, David S. Richardson¹ - Show less +14 more•Institutions (4)

Duke University¹, Lawrence Berkeley National Laboratory², University of North Carolina at Chapel Hill³, University of Manchester⁴

01 Jan 2018-Protein Science

TL;DR: Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by Mol probity's unique all‐atom clashscore.

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Abstract: This paper describes the current update on macromolecular model validation services that are provided at the MolProbity website, emphasizing changes and additions since the previous review in 2010. There have been many infrastructure improvements, including rewrite of previous Java utilities to now use existing or newly written Python utilities in the open-source CCTBX portion of the Phenix software system. This improves long-term maintainability and enhances the thorough integration of MolProbity-style validation within Phenix. There is now a complete MolProbity mirror site at http://molprobity.manchester.ac.uk. GitHub serves our open-source code, reference datasets, and the resulting multi-dimensional distributions that define most validation criteria. Coordinate output after Asn/Gln/His "flip" correction is now more idealized, since the post-refinement step has apparently often been skipped in the past. Two distinct sets of heavy-atom-to-hydrogen distances and accompanying van der Waals radii have been researched and improved in accuracy, one for the electron-cloud-center positions suitable for X-ray crystallography and one for nuclear positions. New validations include messages at input about problem-causing format irregularities, updates of Ramachandran and rotamer criteria from the million quality-filtered residues in a new reference dataset, the CaBLAM Cα-CO virtual-angle analysis of backbone and secondary structure for cryoEM or low-resolution X-ray, and flagging of the very rare cis-nonProline and twisted peptides which have recently been greatly overused. Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by MolProbity's unique all-atom clashscore.

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2,355 citations

Journal Article•DOI•

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

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Qihui Wang¹, Yanfang Zhang¹, Lili Wu¹, Sheng Niu², Sheng Niu¹, Chunli Song¹, Chunli Song³, Zengyuan Zhang¹, Guangwen Lu⁴, Chengpeng Qiao¹, Yu Hu⁵, Yu Hu¹, Kwok-Yung Yuen⁶, Qisheng Wang¹, Huan Zhou¹, Jinghua Yan, Jianxun Qi¹ - Show less +13 more•Institutions (6)

Chinese Academy of Sciences¹, Shanxi Agricultural University², Anhui University³, Sichuan University⁴, University of Science and Technology of China⁵, University of Hong Kong⁶

14 May 2020-Cell

TL;DR: The crystal structure of the C-terminal domain of SARS-CoV-2 (SARS- coV- 2-CTD) spike (S) protein in complex with human ACE2 (hACE2) is presented, which reveals a hACE2-binding mode similar overall to that observed for SARS -CoV.

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2,334 citations

Journal Article•DOI•

Linking crystallographic model and data quality.

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P. Andrew Karplus¹, Kay Diederichs²•Institutions (2)

Oregon State University¹, University of Konstanz²

25 May 2012-Science

TL;DR: Here, it is shown that despite their widespread use, Rmerge values are poorly suited for determining the high-resolution limit and that current standard protocols discard much useful data, and a statistic is introduced that estimates the correlation of an observed data set with the underlying (not measurable) true signal.

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Abstract: In macromolecular x-ray crystallography, refinement R values measure the agreement between observed and calculated data. Analogously, R(merge) values reporting on the agreement between multiple measurements of a given reflection are used to assess data quality. Here, we show that despite their widespread use, R(merge) values are poorly suited for determining the high-resolution limit and that current standard protocols discard much useful data. We introduce a statistic that estimates the correlation of an observed data set with the underlying (not measurable) true signal; this quantity, CC*, provides a single statistically valid guide for deciding which data are useful. CC* also can be used to assess model and data quality on the same scale, and this reveals when data quality is limiting model improvement.

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1,689 citations

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Journal Article•DOI•

A short history of SHELX

[...]

George M. Sheldrick¹•Institutions (1)

University of Göttingen¹

01 Jan 2008-Acta Crystallographica Section A

TL;DR: This paper could serve as a general literature citation when one or more of the open-source SH ELX programs (and the Bruker AXS version SHELXTL) are employed in the course of a crystal-structure determination.

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Abstract: An account is given of the development of the SHELX system of computer programs from SHELX-76 to the present day. In addition to identifying useful innovations that have come into general use through their implementation in SHELX, a critical analysis is presented of the less-successful features, missed opportunities and desirable improvements for future releases of the software. An attempt is made to understand how a program originally designed for photographic intensity data, punched cards and computers over 10000 times slower than an average modern personal computer has managed to survive for so long. SHELXL is the most widely used program for small-molecule refinement and SHELXS and SHELXD are often employed for structure solution despite the availability of objectively superior programs. SHELXL also finds a niche for the refinement of macromolecules against high-resolution or twinned data; SHELXPRO acts as an interface for macromolecular applications. SHELXC, SHELXD and SHELXE are proving useful for the experimental phasing of macromolecules, especially because they are fast and robust and so are often employed in pipelines for high-throughput phasing. This paper could serve as a general literature citation when one or more of the open-source SHELX programs (and the Bruker AXS version SHELXTL) are employed in the course of a crystal-structure determination.

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81,116 citations

"PHENIX: a comprehensive Python-base..." refers methods in this paper

...…Search; Grosse-Kunstleve & Adams, 2003) combines the multi-trial dual-space recycling approaches pioneered by Shake-and-Bake (Miller et al., 1994) and later SHELXD (Sheldrick, 2008) with the use of the fast translation function (Navaza & Vernoslova, 1995; GrosseKunstleve & Brunger, 1999)....
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...The fast translation function is the basis for a systematic search in the Patterson function (performed in reciprocal space), in contrast to the stochastic alternative of SHELXD (performed in direct space)....
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...The substructure-determination procedure implemented as phenix.hyss (Hybrid Substructure Search; Grosse-Kunstleve & Adams, 2003) combines the multi-trial dual-space recycling approaches pioneered by Shake-and-Bake (Miller et al., 1994) and later SHELXD (Sheldrick, 2008) with the use of the fast translation function (Navaza & Vernoslova, 1995; GrosseKunstleve & Brunger, 1999)....
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Journal Article•DOI•

The Protein Data Bank

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Helen M. Berman¹, John D. Westbrook, Zukang Feng, Gary L. Gilliland, Talapady N. Bhat, Helge Weissig, Ilya N. Shindyalov, Philip E. Bourne - Show less +4 more•Institutions (1)

Rutgers University¹

01 Jan 2000-Nucleic Acids Research

TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.

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Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.

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34,239 citations

"PHENIX: a comprehensive Python-base..." refers background in this paper

...This task can be complicated for several reasons: the presence of novel ligands or nonstandard residues in the PDB-format (Berman et al., 2000) coordinate file, data collected from twinned crystals, various reflection datafile formats, different representation of atomic displacement parameters in the presence of TLS (Schomaker & Trueblood, 1968), experimental data type (X-ray and/or neutron), files with multiple models and various formatting issues....
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...This task can be complicated for several reasons: the presence of novel ligands or nonstandard residues in the PDB-format (Berman et al., 2000) coordinate file, data collected from twinned crystals, various reflection datafile formats, different representation of atomic displacement parameters in…...
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Journal Article•DOI•

Coot: model-building tools for molecular graphics.

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Paul Emsley¹, Kevin Cowtan¹•Institutions (1)

University of York¹

01 Dec 2004-Acta Crystallographica Section D-biological Crystallography

TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.

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Abstract: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics. The map-fitting tools are available as a stand-alone package, distributed as `Coot'.

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27,505 citations

"PHENIX: a comprehensive Python-base..." refers background or methods in this paper

...Currently, if an incorrect pucker is diagnosed it must usually be fixed by user rebuilding, for instance in Coot (Emsley & Cowtan, 2004) or in RNABC (Wang et al., 2008)....
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...This allows the interfaces to integrate seamlessly; any model or map in PHENIX can be automatically opened in Coot with a single click....
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...All-atom contacts (Word, Lovell, LaBean et al., 1999) are calculated by phenix.probe, which provides the atomic overlap information needed for the validation of serious all-atom steric clashes and can also be visualized in Coot....
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...The PHENIX GUI includes extension modules for the modeling programs Coot (Emsley & Cowtan, 2004) and PyMOL (DeLano, 2002), both of which are controlled remotely from PHENIX using the XML-RPC protocol....
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...The phenix.refine GUI is integrated with Coot and PyMOL, allowing seamless visual analysis of the refined model and associated maps....
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The PyMOL Molecular Graphics System

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W. L. Delano

01 Jan 2002

19,213 citations

"PHENIX: a comprehensive Python-base..." refers methods in this paper

...In programs that iteratively rebuild or refine structures, such as AutoBuild and phenix.refine, the current model and maps will be continually updated in Coot and/or PyMOL as soon as they are available....
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...The phenix.refine GUI is integrated with Coot and PyMOL, allowing seamless visual analysis of the refined model and associated maps....
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...The PHENIX GUI includes extension modules for the modeling programs Coot (Emsley & Cowtan, 2004) and PyMOL (DeLano, 2002), both of which are controlled remotely from PHENIX using the XML-RPC protocol....
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Journal Article•DOI•

Phaser crystallographic software

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Airlie J. McCoy¹, Ralf W. Grosse-Kunstleve², Paul D. Adams², Martyn Winn³, Laurent C. Storoni¹, Randy J. Read¹ - Show less +2 more•Institutions (3)

University of Cambridge¹, Lawrence Berkeley National Laboratory², Daresbury Laboratory³

01 Aug 2007-Journal of Applied Crystallography

TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.

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Abstract: Phaser is a program for phasing macromolecular crystal structures by both molecular replacement and experimental phasing methods. The novel phasing algorithms implemented in Phaser have been developed using maximum likelihood and multivariate statistics. For molecular replacement, the new algorithms have proved to be significantly better than traditional methods in discriminating correct solutions from noise, and for single-wavelength anomalous dispersion experimental phasing, the new algorithms, which account for correlations between F+ and F−, give better phases (lower mean phase error with respect to the phases given by the refined structure) than those that use mean F and anomalous differences ΔF. One of the design concepts of Phaser was that it be capable of a high degree of automation. To this end, Phaser (written in C++) can be called directly from Python, although it can also be called using traditional CCP4 keyword-style input. Phaser is a platform for future development of improved phasing methods and their release, including source code, to the crystallographic community.

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17,755 citations

"PHENIX: a comprehensive Python-base..." refers background or methods in this paper

...Phaser, available in PHENIX as phenix.phaser, applies the principle of maximum likelihood to solving crystal structures by molecular replacement, by single-wavelength anomalous diffraction (SAD) or by a combination of both....
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...Phenix.automr carries out automated likelihood-based molecular replacement using phenix.phaser (Read, 2001; McCoy et al., 2005, 2007; McCoy, 2007)....
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...More recent builds of PHENIX contain a new GUI for the AutoMR wizard and future releases will include a new interface for Phaser (McCoy et al., 2007)....
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...Phenix.autosol carries out experimental phasing with phenix.phaser (McCoy et al., 2004, 2007) or phenix.solve (Terwilliger & Berendzen, 1999), density modification with phenix.resolve (Terwilliger, 1999) and preliminary model building using the methods in phenix.autobuild (Terwilliger,…...
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...If a molecular-replacement model is available, phenix. autosol will use phenix.phaser (McCoy et al., 2004, 2007) to complete the anomalous substructure iteratively by constructing log-likelihood gradient maps for the anomalous scatterers based on the model of the non-anomalous structure and any…...
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