The Phenix software has been developed as a result of the highly collaborative work of 4 groups located at Lawrence Berkeley Laboratory, Los Alamos National Laboratory, Cambridge University, and Duke University. Building on our prior work we will continue to collaborate in the development of new methods to improve structure solution, with a focus on low (near atomic) resolution (3-4.5). Researchers still encounter significant problems in solving and completing structures in this regime. Improvements in single wavelength anomalous (SAD) phasing, molecular replacement, model building, refinement and validation will make it possible for researchers to tackle more challenging experimental systems. This is particularly timely as new approaches to data collection, such as serial crystallography, are producing lower resolution structures of membrane proteins and large flexible complexes. Recent developments in the field of single particle cryo-electron microscopy (cryo-EM) have generated a rapid growth in the number of large macromolecular complexes solved ab initio. Therefore, a significant area of development for the Phenix team in the next 5 years will be cryo-EM, in particular near atomic resolution single particle image reconstruction. This is one of the most exciting developments in the field of structural biology in recent history. Our goal will be to collaborate to extend our current methods, and develop new ones, to address the problems of model fitting, model building, refinement and validation of atomic models derived from cryo-EM maps.
Overall Narrative X-ray crystallography and increasingly electron microscopy are critical tools in the study of biological systems. They are able to provide information that has been a prerequisite to the understanding the fundamentals of life. Crystallography is also a method that is central to the development of new therapeutics for human disease. The overarching goal of this Program Project is to enable researchers to generate better atomic models than is possible with current methods. This will lead to more insightful biological interpretation and better drugs to improve human health.
| Richardson, Jane S; Williams, Christopher J; Hintze, Bradley J et al. (2018) Model validation: local diagnosis, correction and when to quit. Acta Crystallogr D Struct Biol 74:132-142 |
| Herzik Jr, Mark A; Fraser, James S; Lander, Gabriel C (2018) A Multi-model Approach to Assessing Local and Global Cryo-EM Map Quality. Structure : |
| Kryshtafovych, Andriy; Monastyrskyy, Bohdan; Adams, Paul D et al. (2018) Distribution of evaluation scores for the models submitted to the second cryo-EM model challenge. Data Brief 20:1629-1638 |
| Moriarty, Nigel W; Liebschner, Dorothee; Klei, Herbert E et al. (2018) Interactive comparison and remediation of collections of macromolecular structures. Protein Sci 27:182-194 |
| Kryshtafovych, Andriy; Adams, Paul D; Lawson, Catherine L et al. (2018) Evaluation system and web infrastructure for the second cryo-EM model challenge. J Struct Biol 204:96-108 |
| Terwilliger, Thomas C; Adams, Paul D; Afonine, Pavel V et al. (2018) Map segmentation, automated model-building and their application to the Cryo-EM Model Challenge. J Struct Biol 204:338-343 |
| Williams, Christopher J; Headd, Jeffrey J; Moriarty, Nigel W et al. (2018) MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci 27:293-315 |
| Terwilliger, Thomas C; Adams, Paul D; Afonine, Pavel V et al. (2018) A fully automatic method yielding initial models from high-resolution cryo-electron microscopy maps. Nat Methods 15:905-908 |
| Richardson, Jane S; Williams, Christopher J; Videau, Lizbeth L et al. (2018) Assessment of detailed conformations suggests strategies for improving cryoEM models: Helix at lower resolution, ensembles, pre-refinement fixups, and validation at multi-residue length scale. J Struct Biol 204:301-312 |
| Hintze, Bradley J; Richardson, Jane S; Richardson, David C (2017) Mismodeled purines: implicit alternates and hidden Hoogsteens. Acta Crystallogr D Struct Biol 73:852-859 |
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