Phaser Progress Report (MR)

1. Phaser Progress Report (MR) Airlie McCoy CCP4 Developers’ meeting 17th-19th March 2008

2. Phaser for Molecular Replacement • Results from last year • What we are doing at the moment • Plan…

3. Phaser-2.1.1 12.11.2007 • Default packing criteria relaxed to allow a small number of clashes • Default packing distance increased to identify intercalation of helices • Composition can be estimated from solvent content • Default composition corresponds to 50% solvent • If automated MR search finds some, but not all, components, the partial solution is output • Output of PDB hybrid-36 atom numbers and col(21-22) chainids for largest structures • Improved SAD phasing • SAD phasing starting from MR partial model

4. Distribution • The Phaser-2.1.1 module is available through the CCP4 automated downloads page • Thanks to Martyn • Thanks to Francois for the Windows installer • Also distributed in phenix-1.3b • Already up to phaser-2.1.3 due to a few bugfixes on phaser-2.1 series • Now working on Phaser-2.2 • Changed from cvs to svn: it is much better!

9. Current Developments… • …by the current developers • Gabor Bunkoczi • Automatic detection of model symmetry • Ongoing project of developing MR pipeline (phenix) • Robert Oeffner • Parallelization • Minimizer

10. Symmetry of MR search model • Automatic detection of point group symmetry • User friendly (black box) • Faster and less error-prone than user defined input Symmetric model Multiple identical solutions Waste of time

11. Model Other RNA/DNA Prune solutions Protein E F A B Model symmetry C D Symmetry operation Symmetry operation Symmetry operation Point group Point group

12. Symmetry of MR search model • Algorithm accounts for • breaks in chains • unequal number of residues in chains • All chains in the model must conform to the point group symmetry • Prevents branching of tree search • c.f. Crystallographic symmetry • 30% of the structures in the pdb use crystallographic symmetry to build the biologically active oligomer • Restricts search space

13. Parallelization • Uses OPENMP • Portable, including linux and windows • Distributed with gcc 4.2 and above • Uses compiler directives • Code can be compiled without OPENMP • Biggest GOTCHA is the “race condition” • A race condition is what happens when two threads of execution attempt to modify something at the same time • Can be very difficult to detect and locate • Not always obvious e.g. variable++

14. Race condition

15. Parallelization • Must be done at a level where the overhead of splitting the jobs onto different processors doesn’t negate the effort of doing the spitting • Rice function sum over reflections is unsuitable • Phaser threaded where there is a “progress bar” • LLG calculation in brute force RF and TF • LLG rescoring of top fast RF and TF solutions • LLG for 500 random points in RF and TF (for Z-score) • Elmn calculations for model and data • Ensembling

16. Parallelization • Following discussion on ccp4-dev (initiated by Kevin), the parallelization is accessed via • phaser --jobs 4 • Or phaser -j 4 • (Or keyword JOBS 4) • I can’t live without it now! • But, sorry folks, we are not confident enough to release it just yet • Undetected race conditions?

17. To-do list • MR pipeline (ongoing) • Improvements to minimizer • Relative overall B-factor refinement for models in an MR solution • etc…