Not retired: Hall symbols + CIFor

How Syd influenced my life without me noticing it.

Ralf W. Grosse-Kunstleve

Computational Crystallography InitiativeLawrence Berkeley National Laboratory

White-Hall Retirement Symposium, July 16/17, 2007

My connections to Syd

• PhD project: Zeolite structure determination from powder data using extracted intensities– focus– sginfo: Hall symbols

• Contributions to Xplor/CNS– Joined Axel Brunger’s group encouraged by Syd (ECM

1995)– Single-crystal protein crystallography– About 80% of all PDB entries refined with Xplor/CNS– CNS PDB deposition via mmCIF files

• Phenix project– Automation of protein structure determination– Fresh start after losing a legal battle– The P in Phenix is for Python: recommended by Syd

Concise space group symbols

• Symbols for crystallographic space groups• Designed to overcome limitations of the familiar Hermann-

Mauguin symbols (e.g. P 21 21 21)

• H-M symbols are defined in International Tables for Crystallography– Created by a generation of scientist that didn’t have computers

• Define the space group type uniquely

• But not the exact setting: inadequate for automatic processing• Attempts to add a rule set to H-M symbols leads to

complicated algorithms (never standardized)• H-M symbols cover only a very limited subset of settings that

appear, e.g. in the generation of group-subgroup relations

Hall (1981) symbols

• Symbols for crystallographic space groups• Designed to overcome limitations of the familiar Hermann-

Mauguin symbols (e.g. P 21 21 21)

• H-M symbols are defined in International Tables for Crystallography– Created by a generation of scientist that didn’t have computers

• Define the space group type uniquely

• But not the exact setting: inadequate for automatic processing• Attempts to add a rule set to H-M symbols leads to

complicated algorithms (never standardized)• H-M symbols cover only a very limited subset of settings that

appear, e.g. in the generation of group-subgroup relations

Hall symbols

• Designed for automatic processing– No ambiguities

• Via attached transformation symbols, any setting of any crystallographic space group can be represented (Int. Tab. Vol. B, 2001)

• Applications– Determination of space group type– Automatic determination of allowed origin shifts– Automatic group-subgroup processing– Automatic derivation of twin laws– Primitive setting of centered space groups

• Reduces memory requirements

Translation table Hall Hermann-Mauguin/* 081 */ " P -4", /* P -4 *//* 082 */ " I -4", /* I -4 *//* 083 */ "-P 4", /* P 4/m *//* 084 */ "-P 4c", /* P 42/m *//* 085 */ "-P 4a", /* P 4/n :2 *//* 086 */ "-P 4bc", /* P 42/n :2 *//* 087 */ "-I 4", /* I 4/m *//* 088 */ "-I 4ad", /* I 41/a :2 *//* 089 */ " P 4 2", /* P 4 2 2 *//* 090 */ " P 4ab 2ab", /* P 4 21 2 *//* 091 */ " P 4w 2c", /* P 41 2 2 */

STAR + CIF

• Situation before CIF– Vast, diverse variety of data formats– Need to reformat data all the time is a real impediment to scientific

progress– What does “gof” mean?– What does it mean exactly?

• STAR: Self-defining Text Archival and Retrieval format• Hall, S. R., "The STAR File: A New Format for Electronic Data Transfer and

Archiving," J. Chem. Inf. Comput. Sci. 31, 326-333 (1991).

– Defines format– Framework for defining semantics

• CIF (1991)– Based on STAR, defines semantics– Similar in concept to XML schema, but a decade ahead– CIF is de-facto standard in small molecule crystallography– Macromoleclar community has more difficulties with the

semantics part of CIF

Python

• Situation: forced end of CNS development– Legal reasons

• Axel Brunger wanted Paul Adams and me to continue methods development in a different way

• We started exploring the world around us– We wanted a scripting language like CNS with

additional compiled components

• IUCr meeting Glasgow 1999– Watching solar eclipse with Syd– BTW: use Python

The PHENIX project

Funding: NIH Program Project (NIGMS, PSI), Director - Paul Adams

A collaboration between several groups

CCI APPS

SOLVE / RESOLVE

PHASER

TEXTAL

MolProbity / REDUCE

Computational Crystallography Initiative (LBNL)-Paul Adams, Ralf Grosse-Kunstleve, Pavel Afonine-Nigel Moriarty, Nicholas Sauter, Peter Zwart

Los Alamos National Lab (LANL)-Tom Terwilliger, Li-Wei Hung

Cambridge University -Randy Read, Airlie McCoy

Texas A&M University -Tom Ioerger, Jim Sacchettini, Erik McKee

Duke University - Jane Richardson, David Richardson, Ian Davis

Spectrum of phenix components

• Automated analysis of data quality: phenix.xtriage

• Rapid substructure determination: phenix.hyss

• Phasing: Maximum likelihood – SOLVE, PHASER for SAD

• Density modification: Statistical density modification (RESOLVE)

• Automated model building:– Pattern matching methods (RESOLVE or TEXTAL)

• Structure refinement: phenix.refine (likelihood, annealing, TLS)

• Advanced automation: AutoSol – hkl to map

• Ligand building and fitting: eLBOW, AutoLigand

• Validation and Hydrogens: MolProbity + Reduce

phenix.refine

- Group ADP refinement

- Rigid body refinement

- Restrained refinement (xyz, iso/aniso ADP)

- Automatic water picking

- Bond density

- Unrestrained refinement

- FFT or direct summation

- Hydrogens

- Automatic NCS restraints

- Simulated Annealing

- Occupancies (individual, group)

- TLS refinement

- Twinned data

- X-ray, Neutron, joint X-ray + Neutron refinement

Refinement flowchart

Input data and model processing

Refinement strategy selection

Bulk-solvent, Anisotropic scaling, Twinning parameters refinement

Ordered solvent (add / remove)

Target weights calculation

Coordinate refinement(rigid body, individual)

(minimization or Simulated Annealing)

ADP refinement(TLS, group, individual iso / aniso)

Occupancy refinement (individual, group)

Output: Refined model, various maps, structure factors, complete statistics

PDB model,Any data format (CNS, Shelx, MTZ, …)

Files for COOT, O, PyMol

Repeated several times

Summary

• Hall symbols open the door to automatic processing of crystallographic symmetry

• STAR + CIF enable automation of data flow between researchers and archives

• Our experience with Python suggests: it is a good idea to listen to Syd!

• Syd’s wisdom!… Gnu Xtal System, available as an open source project, … but with the expectation that Sourceforge may be its twilight resting place, afore it's entombed by the sands of time, right alongside The King of Kings.

Acknowledgments

• Syd– for shining the light in the right direction– for showing me Perth

• Phenix developers– P.D. Adams– P. Afonine– T.R. Ioerger– A.J. McCoy– E.W. McKee– N.W. Moriarty– R.J. Read– N.K. Sauter– J.N. Smith– L.C. Storoni– T.C. Terwilliger– P.H. Zwart

• Funding: – LBNL (DE-AC03-76SF00098)

– NIH/NIGMS (1P01GM063210)

– PHENIX Industrial Consortium