We propose renewal of our program project for research into new and more powerful probabilistic direct methods solutions for the phase problem in biological crystallography. Our new objectives are methods that will be effective with single-wavelength data, at lower resolution, for larger structures. Such methods will expedite high-throughput biomolecular structure analysis, and will facilitate investigations of the structures of large, complex assemblies of biomolecules. The new methods will therefore have high impact in the genomics-proteomics- bioinformatics-structure-function-analysis-drug design paradigm of basic biomedical science. Our proposed project has four component projects: I. Direct Methods of Phase Determination II. Algorithmic Development for New Phasing Methods for New Phasing Methods III. Phases in Macromolecular Electron Crystallography IV. Phase Measurements for Macromolecular Crystallography Project I is focused on developing and testing new probabilistic phasing theory by a group led by Herbert Hauptman at HWI. Project II is focused on developing and implementing phasing practice in computer programs written, maintained, and distributed to the biostructural research community by a group headed by Charles Weeks at HWI and William Furey at the University of Pittsburgh. Project III is focused on direct methods phasing in electron crystallography using electron microscope images and diffraction data from thin microcrystals by a group led by Douglas Dorset at HWI. Project IV is focused on phasing using synchroton X-ray crystallographic techniques to exploit (1) Renninger three-beam interference effects to measure triplet phase invariants by a group led by Qun Shen at CHESS and (2) Bijvoet or Friedel pair amplitude differences from large structures with large numbers of anomalously scattering atoms measured with very high energy-resolution by a group led by Steven Ealick at MacCHESS and APS.
| Xu, Hongliang; Hauptman, Herbert A (2004) Statistical approach to the phase problem. Acta Crystallogr A 60:153-7 |
| Hauptman, Herbert A; Langs, David A (2003) The phase problem in neutron crystallography. Acta Crystallogr A 59:250-4 |
| Shen, Qun; Wang, Jun (2003) Recursive direct phasing with reference-beam diffraction. Acta Crystallogr D Biol Crystallogr 59:809-14 |
| Xu, Hongliang; Hauptman, Herbert A (2003) On integrating the techniques of direct methods and SIRAS: the probabilistic theory of doublets and its applications. Acta Crystallogr A 59:60-5 |
| Weeks, Charles M; Adams, Paul D; Berendzen, Joel et al. (2003) Automatic solution of heavy-atom substructures. Methods Enzymol 374:37-83 |
| Shen, Qun; Wang, Jun; Ealick, Steven E (2003) Anomalous difference signal in protein crystals. Acta Crystallogr A 59:371-3 |
| Shen, Qun (2003) Improving triplet-phase accuracy by symmetry observations in reference-beam diffraction measurements. Acta Crystallogr A 59:335-40 |
| Lemke, Christopher T; Smith, G David; Howell, P Lynne (2002) S-SAD, Se-SAD and S/Se-SIRAS using Cu Kalpha radiation: why wait for synchrotron time? Acta Crystallogr D Biol Crystallogr 58:2096-101 |
| Xu, Hongliang; Hauptman, Herbert A; Weeks, Charles M (2002) Sine-enhanced Shake-and-Bake: the theoretical basis and applications to Se-atom substructures. Acta Crystallogr D Biol Crystallogr 58:90-6 |
| Hauptman, Herbert A; Guo, D Y; Xu, Hongliang et al. (2002) Algebraic direct methods for few-atoms structure models. Acta Crystallogr A 58:361-9 |
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