Not retired Hall symbols CIF or How

Not retired: Hall symbols + CIF or How Syd influenced my life without me noticing it. Ralf W. Grosse-Kunstleve Computational Crystallography Initiative Lawrence Berkeley National Laboratory White-Hall Retirement Symposium, July 16/17, 2007

My connections to Syd • Ph. D 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 mm. CIF 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 /* /* /* 081 082 083 084 085 086 087 088 089 090 091 */ */ */ Hall " P -4", " I -4", "-P 4 c", "-P 4 a", "-P 4 bc", "-I 4 ad", " P 4 2", " P 4 ab 2 ab", " P 4 w 2 c", Hermann-Mauguin /* P -4 */ /* I -4 */ /* P 4/m */ /* P 42/m */ /* P 4/n : 2 */ /* P 42/n : 2 */ /* I 4/m */ /* I 41/a : 2 */ /* P 4 21 2 */ /* 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 A collaboration between several groups Computational Crystallography Initiative (LBNL) CCI APPS SOLVE / RESOLVE PHASER TEXTAL Mol. Probity / REDUCE -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 Mc. Coy Texas A&M University -Tom Ioerger, Jim Sacchettini, Erik Mc. Kee Duke University - Jane Richardson, David Richardson, Ian Davis Funding: NIH Program Project (NIGMS, PSI), Director - Paul Adams

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: Auto. Sol – hkl to map • Ligand building and fitting: e. LBOW, Auto. Ligand • Validation and Hydrogens: Mol. Probity + Reduce

phenix. refine - Group ADP refinement - Rigid body refinement - Restrained refinement (xyz, iso/aniso ADP) - Automatic water picking - Bond density - Unrestrained refinement - Automatic NCS restraints - FFT or direct summation - Simulated Annealing - Hydrogens - Occupancies (individual, group) - TLS refinement - Twinned data - X-ray, Neutron, joint X-ray + Neutron refinement

Refinement flowchart PDB model, Any data format (CNS, Shelx, MTZ, …) 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) Repeated several times ADP refinement (TLS, group, individual iso / aniso) Occupancy refinement (individual, group) Output: Refined model, various maps, structure factors, complete Files for COOT, O, Py. Mol

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. Mc. Coy E. W. Mc. Kee N. W. Moriarty R. J. Read N. K. Sauter J. N. Smith L. C. Storoni T. C. Terwilliger P. H. Zwart Funding: – LBNL (DE-AC 03 -76 SF 00098) – NIH/NIGMS (1 P 01 GM 063210) – PHENIX Industrial Consortium